Affinage

LPAR1

Lysophosphatidic acid receptor 1 · UniProt Q92633

Length
364 aa
Mass
41.1 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LPAR1 (LPA1/VZG-1/EDG-2) is the prototypical G protein-coupled receptor for extracellular lysophosphatidic acid, coupling LPA sensing to cytoskeletal remodeling, proliferation, and motility across neural, vascular, skeletal, and epithelial tissues (PMID:8922387, PMID:9600933). It was the first cloned LPA receptor, shown by radioligand binding and pertussis toxin-sensitive Gi activation to confer LPA-dependent cell rounding (PMID:8922387), and a single receptor is necessary and sufficient to reconstitute LPA-dependent G-protein activation, stress fiber formation, neurite retraction, SRE activation, and DNA synthesis (PMID:9600933) with strict ligand specificity for LPA over related lysophospholipids (PMID:9430689). Downstream, LPA1 drives bidirectional control of Rac and migration through Gi versus G13/Rho (PMID:16564043), promotes lamellipodia and Rac1-dependent motility together with autotaxin (PMID:14744855), and engages a Gi/Ca2+/Pyk2/GSK-3 axis that phosphorylates tau and mediates neurite retraction (PMID:16452634). Its signaling is tuned by PKC- and GRK2-mediated phosphorylation and desensitization (PMID:15369458, PMID:19306925) and by dynamin2/Rab5-dependent endocytosis and recycling (PMID:12668728), with the PDZ protein GIPC binding the LPA1 SVV motif to control trafficking from APPL endosomes and restrain Akt-driven proliferation and motility (PMID:23145131). Physiologically, LPA1 is required for cortical neurogenesis and neuronal migration (PMID:21878565), oligodendrocyte and Schwann cell myelination and SC-to-axon segregation (PMID:9717712, PMID:24115248), neonatal olfaction-dependent suckling and peripheral nerve integrity (PMID:11087877), astrocyte proliferation (PMID:17692995), lymphatic vessel development (PMID:18606866), chondrocyte proliferation and cartilage formation via β1-integrin/fibronectin assembly (PMID:27005960), bone development and osteoclast differentiation and resorption (PMID:21569876, PMID:24429286), enteric glial calcium signaling controlling gastrointestinal motility (PMID:35166239), and initiation of neuropathic pain through distinct contributions in Schwann cells, neurons, and microglia (PMID:32929779). In disease, LPA1 drives renal and peritoneal fibrosis through CTGF/TGFβ and cytoskeleton-dependent MRTF activation (PMID:18003779, PMID:23322166) — with antifibrotic efficacy confirmed clinically in IPF (PMID:35303880) — and promotes tumor invasion and metastasis through MMP-9, ZEB1/miR-21, and Src/EGFR transactivation (PMID:21102517, PMID:26098771, PMID:29866927, PMID:34302117). It also mediates vascular responses, producing endothelium/eNOS-dependent vasodilation or, via Gi/COX1-dependent TXA2 release, vasoconstriction (PMID:24249637, PMID:28069828).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Established that LPAR1 is a bona fide cell-surface LPA receptor, defining the molecular entity that transduces extracellular LPA into intracellular signaling.

    Evidence Heterologous overexpression in neuroblastoma with radioligand binding and pertussis toxin dissection

    PMID:8922387

    Open questions at the time
    • G-protein repertoire beyond Gi not yet resolved
    • Endogenous physiological role untested
  2. 1998 High

    Showed a single receptor is necessary and sufficient for the full spectrum of LPA responses with strict ligand specificity, ruling out the need for additional LPA-specific receptors for these outputs.

    Evidence Retroviral reconstitution in neuronal and non-neuronal cell lines, plus yeast pheromone-pathway reporter with a specificity panel

    PMID:9430689 PMID:9600933

    Open questions at the time
    • Did not map which G-proteins drive which response
    • Endogenous tissue context absent
  3. 1998 High

    Linked LPAR1 expression to mature oligodendrocytes during myelination, providing the first cell-type-resolved hint of a physiological role in CNS myelin.

    Evidence In situ hybridization, Northern blot, and jimpy mutant analysis with cell-type markers

    PMID:9717712

    Open questions at the time
    • Expression correlation, not functional requirement
    • No protein-level localization yet
  4. 2000 High

    Demonstrated endogenous requirement for LPA1 in neonatal behavior and peripheral nerve integrity, moving the receptor from a reconstituted activity to a developmental necessity.

    Evidence Constitutive knockout mouse with behavioral, cortical neuroblast, and Schwann cell apoptosis readouts

    PMID:11087877

    Open questions at the time
    • Downstream signaling in each tissue not dissected
    • Partial penetrance (~50% lethality) implies redundancy
  5. 2000 Medium

    Distinguished LPA1 from paralogs LPA2/LPA3 in shared and divergent morphological outputs, and implicated LPA1 in nociception, framing subtype-specific functions.

    Evidence Comparative retroviral expression of three subtypes; intrathecal antisense knockdown with pain behavior

    PMID:10686359 PMID:11040035

    Open questions at the time
    • Antisense gave only partial blockade
    • Cell-type origin of pain signaling unresolved
  6. 2003 High

    Defined LPA1 receptor regulation by agonist-induced dynamin2/Rab5-dependent endocytosis and recycling, establishing how the receptor is trafficked and how trafficking feeds back on signaling.

    Evidence FLAG-tagged LPA1 in HeLa with dominant-negative dynamin2 and Rab5, internalization and SRF assays

    PMID:12668728

    Open questions at the time
    • Adaptor proteins for endocytosis not identified
    • Recycling versus degradation balance unclear
  7. 2005 High

    Identified PKC-mediated phosphorylation as the mechanism of LPA1 homologous and heterologous desensitization, explaining how receptor responsiveness is dampened.

    Evidence Receptor phosphorylation assays with PKC inhibitors, downregulation, and GFP-receptor internalization imaging in C9 cells

    PMID:15369458

    Open questions at the time
    • Phosphorylation sites not mapped
    • Relationship to GRK2-mediated desensitization not integrated
  8. 2004 High

    Established LPA1 as the obligate receptor for autotaxin-LPA-driven cell motility and Rac1-dependent lamellipodia, connecting the ATX-LPA axis to migration.

    Evidence lpa1-/- fibroblasts, Rac1 and lamellipodia assays, Ki16425 antagonism in cancer cells

    PMID:14744855

    Open questions at the time
    • GEF/effector linking LPA1 to Rac1 not identified
  9. 2006 High

    Resolved LPA1's bidirectional control of Rac through Gi versus G13/Rho and defined the Gi/Ca2+/Pyk2/GSK-3 axis driving tau phosphorylation and neurite retraction, providing distinct effector branches.

    Evidence CHO cells with PTX/Gα13 peptide/C3 toxin and Rac assays; neuronal co-IP of Pyk2/GSK-3β with knockdown and tau readout

    PMID:16452634 PMID:16564043

    Open questions at the time
    • Conditions selecting Gi vs G13 dominance in vivo unknown
    • Intermediate kinase wiring incomplete
  10. 2006 Medium

    Reported LPA1 nuclear localization and a ligand-independent structural role at dendritic spines, raising non-canonical functions beyond plasma membrane signaling.

    Evidence Cell fractionation/confocal with integrin and Rho-kinase perturbations; GFP-LPA1 imaging and mEPSC recording in hippocampal neurons

    PMID:16638019 PMID:16716145

    Open questions at the time
    • Intranuclear substrates not identified
    • Physiological significance of nuclear pool untested in vivo
  11. 2007 High

    Demonstrated LPA1 requirement in tissue fibrosis (via CTGF/TGFβ), astrocyte proliferation, and endothelial inflammatory gene induction, expanding the receptor into pathological and inflammatory programs.

    Evidence lpa1-/- mice in ureteral obstruction with Ki16425 and CTGF assays; lpa1-null astrocyte proliferation; HUVEC siRNA with ICAM-1 and adhesion assays

    PMID:17692995 PMID:17923111 PMID:18003779

    Open questions at the time
    • Cell-type origin of profibrotic signaling within kidney unresolved
    • Endothelial findings rely on single-lab siRNA
  12. 2008 Medium

    Established cross-talk of LPA1 with EGFR/SphK1 and a developmental role in lymphatic vessel formation, linking the receptor to growth-factor pathways and vasculogenesis.

    Evidence LPA1 siRNA/antagonist with EGFR inhibitor and SphK1 readouts in cancer cells; zebrafish morpholino with mRNA and vegf-c rescue

    PMID:18606866 PMID:18701480

    Open questions at the time
    • Mechanism of EGFR transactivation not fully defined here
    • Lymphatic phenotype based on morpholino
  13. 2009 Medium

    Identified RalA and GRK2 as LPA1-associated regulators, connecting receptor desensitization to a novel RalA-GRK2 complex and PLC activity.

    Evidence Reciprocal co-IP, RalA and PLC activation assays, GRK2 functional assay in HEK293

    PMID:19306925

    Open questions at the time
    • Single lab, no in vivo confirmation
    • Functional consequence of RalA-GRK2 complex unclear
  14. 2011 High

    Defined opposing apoptotic outcomes (epithelial anoikis versus fibroblast survival) and a role in cortical neurogenesis via GRK2-controlled LPA1 overactivation, sharpening context-dependent LPA1 outputs.

    Evidence lpa1-/- bleomycin lung injury with apoptosis assays; ex vivo/in vivo cortical models with GRK2, N-cadherin, and migration readouts; bone-mass phenotyping

    PMID:21569876 PMID:21878565 PMID:22021336

    Open questions at the time
    • Determinants of pro- vs anti-apoptotic outcome unresolved
    • Bone osteoclast role left ambiguous here
  15. 2012 Medium

    Identified GIPC as a direct PDZ-motif binding partner controlling LPA1 endosomal sorting and restraining Akt-driven proliferation/motility, providing a trafficking-signaling link.

    Evidence Co-IP, colocalization on APPL endosomes, GIPC siRNA with Akt, proliferation, and motility assays

    PMID:23145131

    Open questions at the time
    • Single lab without reciprocal in vivo validation
    • Other PDZ partners not surveyed
  16. 2013 High

    Mechanistically tied LPA1 to fibrosis via cytoskeleton-driven MRTF/CTGF transcription, to tumor invasion via MMP-9, and to endothelium-dependent vasodilation, integrating effector pathways into disease phenotypes.

    Evidence lpa1-/- peritoneal fibrosis with MRTF inhibitor; HCC invasion with siRNA/PI3K/p38; aortic ring assays with eNOS-/- and LPA1 antagonists

    PMID:21102517 PMID:23322166 PMID:24249637

    Open questions at the time
    • MRTF-A vs -B specific contributions not separated
    • Vasodilation/constriction switch mechanism only partly defined
  17. 2014 High

    Established LPA1 requirement for Schwann cell migration/myelination and for osteoclast differentiation/resorption, with paclitaxel neuropathic pain dependence, broadening developmental and pathological roles.

    Evidence lpa1-/- ultrastructure and SC migration with HPLC/MS LPA detection; osteoclastogenesis knockouts/antagonists with NFATc1 and resorption readouts; Lpar1-/- paclitaxel pain with LC-MS/MS

    PMID:24115248 PMID:24429286 PMID:25411045

    Open questions at the time
    • Discrepancy with earlier no-osteoclast-effect report unresolved
    • Effector wiring in Schwann cells partial
  18. 2015 Medium

    Extended LPA1 to keratinocyte differentiation/barrier function, MSC migration, chondrocyte/cartilage formation, breast cancer metastasis, and antidepressant ERK signaling, mapping convergent PKC/Rho/integrin effector modules.

    Evidence Keratinocyte siRNA with RHO-ROCK-SRF inhibitors and 3D skin; hMSC migration siRNA cascade; zebrafish/mouse ATX-LPA1 cartilage targeting; LPA1/ZEB1/miR-21 breast cancer cascade; glial ERK transactivation studies

    PMID:25376707 PMID:26098771 PMID:27005960 PMID:27605627 PMID:30447238

    Open questions at the time
    • Several rest on single-lab siRNA
    • Tissue-specific effector selection not unified
  19. 2018 Medium

    Defined hypoxia-driven LPA1/Src/EGFR(Y845)/PI3K-Akt invadopodia signaling and demonstrated synergy of combined LPA1+EGFR blockade in metastasis, refining the oncogenic transactivation mechanism.

    Evidence Pharmacological LPA1/EGFR inhibition, phospho-Y845-EGFR imaging, invasion and in vivo metastasis assays

    PMID:29866927

    Open questions at the time
    • No genetic LPA1 validation in this model
    • Single lab
  20. 2019 Medium

    Implicated LPA1 in microglial activation/NF-κB-driven ischemic brain damage and in RhoA/ROCK2-dependent neuronal apoptosis, connecting the receptor to neuroinflammation and cell death.

    Evidence tMCAO with AM095 and LPA1 shRNA, microglial and MAPK/Akt readouts; LPA-stimulated SH-SY5Y/BV2 co-culture apoptosis (pharmacological only)

    PMID:31145906 PMID:31429777

    Open questions at the time
    • Neuronal apoptosis study lacks receptor-specific genetic validation (Low confidence)
    • Microglia-intrinsic vs extrinsic contribution unresolved
  21. 2021 High

    Demonstrated cell-type-specific LPA1 contributions to neuropathic pain and platelet-LPA-driven osteosarcoma metastasis, providing rigorous genetic causality and therapeutic proof-of-concept.

    Evidence Lpar1 conditional knockouts with four cre lines in nerve ligation pain; CRISPR LPAR1 KO and oral antagonist in osteosarcoma metastasis

    PMID:32929779 PMID:34302117

    Open questions at the time
    • Distinct mechanisms in each pain-relevant cell type not fully delineated
  22. 2022 High

    Established enteric glial LPA1 control of gastrointestinal motility (with human CIPO correlation) and clinical antifibrotic efficacy of LPA1 blockade in IPF, translating mechanism to human disease.

    Evidence LPAR1 calcium imaging in enteric glia with AM966 and human tissue; Scar-in-a-Jar fibrogenesis and serum ECM-neoepitope biomarkers in a phase 2 IPF trial

    PMID:35166239 PMID:35303880

    Open questions at the time
    • Glia-to-neuron signaling intermediary in gut undefined
    • Clinical biomarker effect not yet tied to hard outcomes

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LPA1 selects among its many G-protein and effector branches in a tissue- and context-specific manner, and the identity and function of its intranuclear substrates, remain unresolved.
  • No structural model of context-dependent effector coupling
  • Nuclear LPA1 substrates unidentified
  • No unifying account of pro- vs anti-survival outcomes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 3
Partners
GIPCGRK2GSK-3BPYK2RALA

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 VZG-1 (LPAR1) is a G protein-coupled receptor for lysophosphatidic acid: overexpression increased specific [3H]-LPA membrane binding, induced LPA-dependent cell rounding, and activated Gi (blocked by pertussis toxin), identifying it as the first cloned LPA receptor. Heterologous overexpression in neuroblastoma cell line, radioligand binding assay, pertussis toxin treatment, Western blot The Journal of cell biology High 8922387
1998 A single LPAR1/VZG-1 receptor is necessary and sufficient to mediate multiple LPA-dependent responses—[3H]-LPA binding, G protein activation, stress fiber formation, neurite retraction, SRE activation, and increased DNA synthesis—in both neuronal and non-neuronal cell lines. Heterologous retroviral expression in B103 neuroblastoma and COS-7 cells, functional assays for each response, loss-of-function and gain-of-function comparison Proceedings of the National Academy of Sciences of the United States of America High 9600933
1998 Human LPAR1/EDG-2 expressed in Saccharomyces cerevisiae couples to the yeast heterotrimeric G-protein and activates the pheromone-response MAPK pathway selectively in response to LPA but not to other lyso-glycerophospholipids, sphingosine-1-phosphate, or diacyl-glycerophospholipids, demonstrating high ligand specificity. Heterologous expression in yeast, FUS1::lacZ reporter gene assay, pharmacological specificity panel The Journal of biological chemistry High 9430689
1998 LPAR1/VZG-1 mRNA is expressed selectively in mature oligodendrocytes during postnatal myelination in the murine brain, as demonstrated by co-expression with the mature oligodendrocyte marker PLP but not with astrocyte marker GFAP, and reduced expression in jimpy mice with defective oligodendrocyte differentiation. In situ hybridization, Northern blot, double-label in situ hybridization with PLP and GFAP probes, jimpy mutant mouse analysis The Journal of comparative neurology High 9717712
1998 The lpa1/vzg-1/Gpcr26 gene has a five-exon genomic structure with one intron in the coding region for transmembrane domain VI; both exons 1 and 4 map to proximal murine Chromosome 4, with a partial duplication on Chromosome 6 in Mus spretus. 3′-RACE, genomic clone analysis, backcross mapping, Southern blot Genomics Medium 9721207
2000 Targeted deletion of lpa1 in mice results in ~50% neonatal lethality due to impaired suckling behavior caused by defective olfaction, loss of LPA responsivity in embryonic cortical neuroblasts, and increased apoptosis in sciatic nerve Schwann cells, demonstrating that endogenous LPA-LPA1 signaling is required for normal neonatal behavior and peripheral nerve integrity. Targeted gene deletion (knockout mouse), behavioral suckling assay, embryonic cortical neuroblast LPA response assay, apoptosis analysis in sciatic nerve Proceedings of the National Academy of Sciences of the United States of America High 11087877
2000 Comparative retroviral expression of LPA1, LPA2, and LPA3 in B103 neuroblastoma cells showed that LPA1 and LPA2 mediate cell rounding while LPA3 mediates neurite elongation and inhibits LPA1/LPA2-dependent cell rounding; all three couple to multiple G-proteins and activate IP production, MAPK, and arachidonic acid release while inhibiting cAMP. Retroviral heterologous expression, cell morphology assays, inositol phosphate assay, MAPK assay, cAMP assay, arachidonic acid release assay Molecular pharmacology High 11040035
2000 VZG-1/LPAR1 expressed in dorsal root ganglia mediates LPA-induced nociception at peripheral nociceptor endings, as shown by partial blockade of LPA-elicited pain behavior by intrathecal antisense oligodeoxynucleotides against vzg-1. Intrathecal antisense oligodeoxynucleotide knockdown in mice, intraplantar LPA injection nociception assay, RT-PCR for vzg-1 in DRG Brain research. Molecular brain research Medium 10686359
2002 LP(A1) protein localizes to the cell membrane and processes of oligodendrocytes in culture and in brain slices, co-localizing with myelin basic protein (MBP) and appearing before myelin/oligodendrocyte glycoprotein (MOG), consistent with a role in myelin formation; confirmed by a specific polyclonal antibody validated in LPA1-overexpressing cells versus wild-type. Western blot with receptor-specific polyclonal antibody, immunohistochemistry in glial cultures and rat/human brain slices, co-localization with MBP and GFAP markers Glia Medium 11948806
2003 LPA1 undergoes agonist-induced endocytosis via a dynamin2- and Rab5-dependent pathway: ~40% of surface LPA1 internalizes within 15 min of LPA treatment in a dose-dependent, LPA-specific manner, with receptor recycling upon agonist removal; dominant-negative dynamin2-K44A and Rab5a-S34N both inhibit internalization and mildly attenuate LPA1-dependent SRF activation. Stable expression of FLAG-tagged LPA1 in HeLa cells, dominant-negative mutant expression (dynamin2-K44A, Rab5a-S34N), cell-surface receptor internalization assay, SRF reporter assay Journal of cell science High 12668728
2003 LPA signals through LPA1 in ovarian theca cells to activate ERK1/2 via a non-canonical pathway requiring Rho GTPase but not Gi or Ras, contrasting with EGF-induced ERK activation that requires Gi/Ras. ERK1/2 phosphorylation assay, pertussis toxin treatment, manumycin A (Ras inhibitor), C3 exotoxin lipofection (Rho inhibitor), LPA1/edg2 antibody labeling, RT-PCR Molecular endocrinology (Baltimore, Md.) Medium 12730329
2004 LPA and autotaxin (ATX/lysophospholipase D) stimulate cell motility specifically through LPA1: fibroblasts from lpa1−/− mice lose LPA- and ATX-stimulated motility entirely; LPA-stimulated lamellipodia formation and Rac1 activation are markedly diminished in lpa1−/− cells; motility in cancer cell lines expressing LPA1 is attenuated by the LPA1-selective antagonist Ki16425. Knockout mouse fibroblasts (lpa1−/−, lpa2−/−), cell motility assay, lamellipodia formation assay, Rac1 activation assay, Ki16425 pharmacological inhibition in human cancer cell lines The Journal of biological chemistry High 14744855
2005 LPA1 receptor is phosphorylated by PKC (homologous and heterologous desensitization): phorbol ester-induced PKC activation causes rapid, sustained LPA1 phosphorylation (~2-fold, t1/2 ~1 min) and receptor internalization; PKC inhibitors block both phosphorylation and functional desensitization (inhibition of IP production, Ca2+ rise, and adenylate cyclase inhibition). Receptor phosphorylation assay in C9 cells, PKC inhibitors (bisindolylmaleimide), phorbol ester treatment, PKC downregulation, GFP-tagged receptor internalization imaging The Biochemical journal High 15369458
2006 LPA1 signals through Gi-linked PIP2 hydrolysis and Ca2+ mobilization to activate the tyrosine kinase Pyk2, which forms a complex with GSK-3β and mediates tyrosine phosphorylation and activation of GSK-3, leading to tau phosphorylation and contributing to neurite retraction. Neuronal cell LPA1 expression, co-immunoprecipitation of Pyk2/GSK-3β, Pyk2 knockdown/inactivation, GSK-3 inhibition, tau phosphorylation assay, neurite retraction assay, Ca2+ mobilization assay Molecular biology of the cell High 16452634
2006 LPA1 constitutively localizes in the nucleus of mammalian cells and also traffics from cell membranes to the nucleus in response to LPA; nuclear localization is regulated by cell-matrix interactions through integrin signaling (disrupted by RGDS peptide, enhanced by fibronectin adhesion), and requires Rho kinase and myosin light chain kinase activity; nuclear LPA1 triggers phosphorylation of several intranuclear proteins. Cell fractionation, confocal imaging of GFP-LPA1, RGDS peptide treatment, fibronectin vs. polylysine adhesion comparison, Rho kinase inhibitor (Y27632), MLCK inhibitor (ML9), isolated nuclei kinase assay The Biochemical journal Medium 16716145
2006 In the absence of Gi function (PTX treatment), LPA acting through LPA1 in CHO cells activates G13 and Rho to inhibit Rac activity, lamellipodia formation, and IGF-I-stimulated cell migration; without PTX, LPA stimulates Rac and migration, demonstrating Gi-dependent versus G13/Rho-dependent bidirectional control of Rac by LPA1. CHO cells expressing LPA1 only, pertussis toxin treatment, Gα13 C-terminal peptide expression, C3 toxin, dominant-negative Rac expression, Rho kinase inhibitor, Rac activation assay, cell migration assay Experimental cell research High 16564043
2006 LPA1 overexpressed in hippocampal neurons accumulates in puncta on dendrites and causes increased dendritic spine density and larger spines in a ligand-binding-independent manner, suggesting a structural role in synapse formation and modulation. GFP-LPA1 overexpression in cultured hippocampal neurons, confocal imaging, spine density quantification, ligand-binding-defective mutant expression, miniature EPSC recording Journal of neurochemistry Medium 16638019
2006 LPA1 mediates LPA-induced IL-6 secretion in human aortic smooth muscle cells through a PKC-dependent p38α MAPK pathway, independent of EGF receptor transactivation; siRNA depletion of LPA1 and of p38α both abolished IL-6 secretion. siRNA knockdown of LPA1, PKC inhibitors, p38 MAPK inhibitors, siRNA depletion of p38α, cytokine ELISA and mRNA analysis American journal of physiology. Heart and circulatory physiology Medium 20044439
2007 LPA1 receptor activation promotes renal tubulointerstitial fibrosis: LPA1−/− mice showed significantly attenuated fibrosis (reduced collagen III, α-SMA, F4/80) after ureteral obstruction; pharmacological blockade with Ki16425 similarly reduced fibrosis and decreased CTGF and TGFβ expression; in vitro, LPA rapidly increased CTGF expression in a Ki16425-inhibitable manner. LPA1−/− knockout mice, unilateral ureteral obstruction model, Ki16425 pharmacological antagonism, RT-PCR, collagen III/α-SMA/F4/80 expression analysis, in vitro CTGF assay Journal of the American Society of Nephrology : JASN High 18003779
2007 LPA1 mediates LPA-induced astrocyte proliferation (DNA synthesis): LPA fails to stimulate DNA synthesis in astrocytes from lpa1-null mice despite normal expression of LPA2–5, while LPA1-independent inhibition of glutamate uptake is preserved. Primary cortical astrocytes from lpa1−/− mice, [3H]-thymidine incorporation assay, glutamate uptake assay, qRT-PCR for LPA receptor subtypes Neurochemistry international High 17692995
2007 LPA induces ICAM-1 expression and monocyte adhesion in HUVECs through LPA1; siRNA knockdown of LPA1 significantly suppressed LPA-induced ICAM-1 mRNA, protein, and cell surface expression, and reduced subsequent U937 monocyte adhesion; LPA1 and LPA3 together mediate LPA-enhanced IL-1β, IL-8, and MCP-1 expression. siRNA knockdown of LPA1 and LPA3 in HUVECs, RT-PCR, Western blot, cell surface expression assay, monocyte adhesion assay, chemotaxis assay Biochemical and biophysical research communications Medium 17923111
2008 LPA1 cross-talks with EGFR: LPA through LPA1 markedly upregulates SphK1 mRNA/protein (but not SphK2) in gastric and other cancer cells expressing LPA1; LPA1 receptor antagonism or downregulation prevents SphK1 and S1P3 upregulation; EGFR transactivation by LPA is required for SphK1 induction; SphK1 downregulation attenuates LPA-stimulated migration and invasion. LPA1 antagonist, LPA1 siRNA knockdown, SphK1/SphK2 mRNA/protein analysis, EGFR inhibitor AG1478, SphK1 siRNA knockdown, migration/invasion assays Cancer research Medium 18701480
2008 LPA1 is essential for lymphatic vessel (thoracic duct) development in zebrafish: morpholino knockdown of zlpa1 caused absence of thoracic duct and pericardial/trunk edema in a dose-dependent manner, rescued by ectopic zlpa1 expression and partially by vegf-c overexpression. Morpholino knockdown in zebrafish embryos, rescue by ectopic zlpa1 mRNA, vegf-c overexpression rescue, whole-mount in situ hybridization FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 18606866
2008 LPA1 is required for LPA1 receptor-mediated ERK phosphorylation in Abeta-fiber reorganization after partial sciatic nerve injury: LPA1-knockout mice showed markedly reduced ERK phosphorylation in superficial spinal dorsal horn following Abeta-fiber stimulation post-injury, implicating LPA1 in spinal circuit reorganization underlying neuropathic allodynia. LPA1−/− knockout mice, partial sciatic nerve ligation, pERK immunohistochemistry in spinal dorsal horn, quantitative analysis of pERK-positive cells Molecular pain Medium 18854053
2009 RalA small GTPase associates with LPA1 and LPA2, and LPA stimulation of LPA1 activates RalA; LPA1-mediated signaling promotes Ral-dependent phospholipase C activity; GRK2 is required for desensitization of LPA1, and LPA1 activity promotes formation of a novel RalA–GRK2 complex. Co-immunoprecipitation of RalA with LPA1/LPA2 in HEK293 cells, RalA activation assay, phospholipase C activity assay, GRK2 functional assay, protein complex detection Cellular signalling Medium 19306925
2010 LPA1 and LPA3 promote neointima formation through induction of HIF-1α and CXCL12 expression, mobilization of Sca-1+/Lin− smooth muscle progenitor cells, and their neointimal recruitment; Ki16425 inhibited neointima formation by 71% and blocked SPC mobilization and recruitment, confirmed by LPA1- and LPA3-specific siRNA and CXCR4 antagonist. Wire-induced carotid injury in apoE−/− mice, Ki16425 pharmacological antagonism, LPA1/3-specific siRNA, bone marrow chimeric mice with SM22-LacZ transgenic cells, 2-photon microscopy, immunostaining, qRT-PCR Circulation research High 20360252
2011 LPA1 promotes epithelial cell apoptosis (specifically anoikis) after lung injury: LPA1-deficient mice showed significantly fewer apoptotic epithelial cells and reduced caspase-3 activity 3 days after bleomycin; in cultured bronchial epithelial cells, LPA-LPA1 signaling induced anoikis; LPA negatively regulated epithelial cell attachment. Conversely, LPA-LPA1 signaling promoted fibroblast resistance to apoptosis. LPA1−/− knockout mice, bleomycin lung injury model, TUNEL/apoptosis quantification, caspase-3 activity assay, human bronchial epithelial cell culture, attachment assay, R3/1 alveolar epithelial cell assay American journal of respiratory cell and molecular biology High 22021336
2011 LPA1 deficiency results in abnormal bone development and decreased bone mass (osteoporosis in trabecular and cortical bone), with reduced osteoblastic differentiation of bone marrow mesenchymal progenitors and sternal/costal abnormalities; no clear modification of osteoclasis was detected. LPA1−/− knockout mice, microcomputed tomography, histological analysis, bone marrow mesenchymal progenitor osteoblastic differentiation assay Bone Medium 21569876
2011 Fetal hypoxia induces cortical disruption via overactivation of LPA1 signaling: hypoxia selectively inhibited GRK2 expression, leading to LPA1 overactivation, N-cadherin disruption, displacement of mitotic NPCs, and impaired neuronal migration; genetic removal or pharmacological inhibition of LPA1 prevented these hypoxia-induced cortical defects; downstream pathways include Gαi and Rac1. Ex vivo cortical slice cultures and in vivo mouse models, LPA1−/− knockout, LPA1 pharmacological inhibition, GRK2 expression analysis, N-cadherin disruption assay, NPC displacement quantification, neuronal migration assay Proceedings of the National Academy of Sciences of the United States of America High 21878565
2012 GIPC PDZ protein directly binds the SVV PDZ-binding motif of LPA1 (but not other LPA receptors), colocalizes and co-immunoprecipitates with LPA1 on APPL signaling endosomes; GIPC depletion by siRNA disturbs LPA1 trafficking from APPL endosomes to EEA1 early endosomes and promotes LPA1-mediated Akt signaling, cell proliferation, and motility. Co-immunoprecipitation, colocalization imaging, siRNA GIPC depletion, Akt signaling assay, cell proliferation and motility assays PloS one Medium 23145131
2013 LPA1 activation on mesothelial cells induces cytoskeleton reorganization, causing nuclear translocation of MRTF-A and MRTF-B, which drives CTGF expression in a paracrine fashion to promote fibroblast proliferation; LPA1 genetic deletion or pharmacological antagonism reduced peritoneal fibrosis by >50%; pharmacological inhibition of MRTF-induced transcription also attenuated CTGF expression and fibrosis. LPA1−/− knockout mice, peritoneal fibrosis model, Ki16425 pharmacological antagonism, MRTF nuclear translocation imaging, CTGF expression assay, paracrine fibroblast proliferation assay, MRTF transcription inhibitor FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 23322166
2013 LPA1 mediates LPA-induced MMP-9 expression and hepatocellular carcinoma cell invasion via coordinate activation of PI3K and p38 MAPK; LPA1 silencing or pharmacological inhibition attenuated MMP-9 expression and invasion; MMP-9 reduction also blocked LPA-induced invasion, placing MMP-9 downstream of LPA1. LPA1 siRNA knockdown, pharmacological LPA1 inhibition, PI3K inhibitor, dominant-negative PKCδ and p38 MAPK mutants, MMP-9 expression assay, invasion assay Oncogene Medium 21102517
2013 LPA1 mediates LPA-induced vasodilation in mouse aorta via endothelium-dependent mechanism requiring phospholipase C and eNOS; endothelium removal or eNOS genetic deletion converted vasodilation to vasoconstriction; LPA1 antagonist AM095 and LPA1 genetic deletion abolished LPA-induced vasorelaxation; LPA2 deletion had no effect. Thoracic aorta ring assay, endothelium denudation, eNOS−/− knockout mice, LPA1−/− and LPA2−/− knockout mice, LPA1 antagonists (Ki16425, AM095), PLC inhibitors (U73122, edelfosine), PI3K inhibitors FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 24249637
2013 LPA1 is required for embryonic Schwann cell migration and peripheral myelination: LPA1-null mice show delayed SC-to-axon segregation, polyaxonal myelination, and thinner myelin sheaths; in primary culture, LPA promotes SC migration through LPA1; Gαi and Rac1 are key downstream signaling components of LPA1 in SCs; dorsal root ganglia neurons produce LPA (detected by HPLC/MS). LPA1−/− knockout mice, ultrastructural analysis of peripheral nerves, primary SC migration assay, conditioned media HPLC/MS LPA detection, Gαi and Rac1 downstream signaling analysis Glia High 24115248
2014 LPA1 is essential for osteoclast differentiation and bone resorption: Lpar1−/− mice have reduced osteoclastogenesis; LPA1 antagonists (Ki16425, Debio0719, VPC12249) inhibit osteoclast differentiation and NFATc1 expression; LPA1 blockade interferes with osteoclast precursor fusion but not proliferation; mature LPA1−/− osteoclasts have reduced podosome belt/sealing zone and diminished matrix resorption; LPA1 expression increases in ovariectomized mouse bone and Debio0719 prevents ovariectomy-induced bone loss. Lpar1/2/3−/− knockout bone marrow osteoclastogenesis assay, pharmacological LPA1 antagonists, NFATc1 and DCSTAMP expression analysis, podosome belt/sealing zone microscopy, mineralized matrix resorption assay, ovariectomy model, intravital multiphoton microscopy The Journal of biological chemistry High 24429286
2014 Paclitaxel-induced neuropathic pain requires LPA1/LPA3-mediated amplification of spinal LPA production: paclitaxel triggers spinal LPA (18:1-, 16:0-, 18:0-LPA) production dependent on NK1 and NMDA receptors; this LPA production and resulting mechanical allodynia are absent in Lpar1−/− and Lpar3−/− mice; NK1 and NMDA receptor antagonists block both LPA production and allodynia. Lpar1−/− and Lpar3−/− knockout mice, intrathecal receptor antagonists, LC-MS/MS LPA quantification, behavioral nociception assay Molecular pain Medium 25411045
2015 LPA induces FLG (filaggrin) expression in human keratinocytes via LPAR1 and LPAR5 receptors and downstream RHO-ROCK-SRF pathway; comprehensive gene profiling showed LPA facilitates broader keratinocyte differentiation; LPA promotes barrier function in a 3D skin model and in mouse skin in vivo. LPAR1/5 receptor siRNA knockdown in keratinocytes, RHO-ROCK-SRF pathway inhibitors, gene expression profiling, 3D skin culture model, in vivo mouse skin treatment The Journal of investigative dermatology Medium 30447238
2015 ATX-LPA1 signaling promotes chondrocyte proliferation and cartilage formation: loss of ATX-LPA1 signaling (gene targeting in zebrafish and mice) leads to chondrocyte disorganization and severe cartilage defects; mechanistically, LPA1 promotes S-phase entry through β1-integrin translocation, leading to fibronectin assembly, extracellular matrix deposition, and chondrocyte-matrix adhesion. Gene targeting in zebrafish and mice (ATX and LPA1 knockouts), cell proliferation and S-phase entry assays, β1-integrin translocation assay, fibronectin assembly assay, in vivo cartilage histology Scientific reports High 27005960
2015 LPA1 mediates the LPA1/ZEB1/miR-21 axis in basal breast cancer: LPA via LPA1 and PI3K up-regulates ZEB1, which in turn drives miR-21 expression; miR-21 inhibitor, LPA1 silencing, or ZEB1 silencing all block LPA-induced migration in vitro and tumor bone colonization in vivo. siRNA knockdown of LPA1 and ZEB1, PI3K inhibitor, miR-21 inhibitor/mimic, in vitro migration/invasion assays, in vivo tumor cell bone colonization model Oncotarget Medium 26098771
2015 Autotaxin-LPA1/3 signaling promotes hMSC migration via LPAR1/3-dependent PKC activation, downstream bifurcation into PKC/GSK3β/β-catenin (E-cadherin reduction) and PKC/Rac1/CDC42 (F-actin reorganization) pathways; LPA1/3 siRNA, Gαi and Gαq knockdown, and pertussis toxin all blocked migration. siRNA knockdown of LPAR1/3, Gαi and Gαq, β-catenin, Rac1, CDC42; PKC inhibitors; β-catenin nuclear translocation assay; CDH-1 promoter reporter; F-actin imaging; in vivo wound healing model Stem cells (Dayton, Ohio) Medium 25376707
2016 ATX-LPA1 signaling promotes chondrocyte S-phase entry through β1-integrin translocation and fibronectin assembly (also established in 2016 Nishioka et al.), and LPA1 in mesenchymal cells signals via Gαi and Gαq to regulate cell migration; LPA1 mediates antidepressant-induced ERK1/2 activation in glial cells through Gi-FGF receptor transactivation-PDGF receptor transactivation axis. LPA1 siRNA in C6 glioma cells and rat astrocytes, AM966 LPA1-selective antagonist, pertussis toxin, FGF-R and PDGF-R tyrosine kinase inhibitors, ERK/CREB/Elk-1 phosphorylation assay, cell viability/apoptosis assay The Journal of pharmacology and experimental therapeutics Medium 27605627
2017 LPA1-mediated vasoconstriction in vascular smooth muscle cells occurs via Gi-dependent, COX1-mediated autocrine/paracrine TXA2 release and consequent TP receptor activation: LPA1−/− and COX1−/− mice both lack VPC31143-induced vasoconstriction and TXA2 release; LPA2 deletion or LPA3 inhibition had no effect. LPA1−/−, LPA2−/−, COX1−/−, TP−/− knockout mice, endothelium-denuded aorta ring assay, TXA2 release measurement, pertussis toxin treatment, Ki16425 antagonism FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 28069828
2018 Under hypoxia, LPA1 mediates invadopodia production and metastasis in cancer cells through Src-mediated transactivation of EGFR (Y845 phosphorylation), leading to PI3K/Akt activation; combined EGFR and LPA1 inhibition synergistically suppressed metastasis in vivo. LPA1 pharmacological inhibition, EGFR inhibition, phospho-Y845-EGFR immunostaining in hypoxic tumor zones, invasion assay, in vivo metastasis model Molecular cancer research : MCR Medium 29866927
2019 LPA1 mediates microglial activation and brain damage after transient focal cerebral ischemia: LPA1 antagonist AM095 and LPA1 shRNA lentivirus both attenuated brain infarction, reduced microglial activation and NF-κB activation; LPA1 suppression decreased MAPK activation and increased Akt phosphorylation in ischemic brain. tMCAO mouse model, AM095 pharmacological antagonist, lentiviral LPA1 shRNA, immunohistochemistry for microglial markers, qRT-PCR for proinflammatory cytokines, Western blot for MAPK/Akt, in vitro LPS-stimulated primary microglia Journal of neuroinflammation Medium 31429777
2019 LPA1 induces neuronal apoptosis through the RhoA/ROCK2 signaling pathway downstream of LPA receptor activation: LPA1-dependent neuronal apoptosis involves RhoA, ROCK2, p-p38, p-ERK, and NF-κB/IκBα; Saikosaponin-d (SSd) decreases LPA1 protein in hippocampus and suppresses this pathway. LPA1 protein expression in vivo (hippocampus), Western blot for RhoA/ROCK2/MAPKs/NF-κB in LPA-stimulated SH-SY5Y cells, co-culture with LPS-stimulated BV2 microglia, apoptosis analysis Neuropharmacology Low 31145906
2020 Conditional cell-type-specific deletion of Lpar1 using nestin-, synapsin-, P0- (Schwann cell), and CD11b- (microglial) cre lines all reduced neuropathic pain responses in the partial sciatic nerve ligation model, demonstrating that LPA1 in Schwann cells, neurons, and microglia each contribute to neuropathic pain initiation through distinct mechanisms. Lpar1flox/flox conditional knockout crossed with nestin-cre, synapsin-cre, P0-cre, CD11b-cre; partial sciatic nerve ligation pain model; behavioral pain assays FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 32929779
2021 LPA1 (LPAR1) mediates platelet-derived LPA-induced osteosarcoma invasion and pulmonary metastasis: LPAR1 knockout in osteosarcoma cells abolished platelet-mediated invasion in vitro and early pulmonary metastatic foci in vivo; oral LPAR1 antagonist ONO-7300243 prevented pulmonary metastasis in mouse models. LPAR1 gene KO in osteosarcoma cells (CRISPR), platelet activation assay, invasion assay, experimental pulmonary metastasis model, pharmacological LPAR1 antagonism Oncogene High 34302117
2022 LPA1 expressed in enteric glia mediates gastrointestinal motility: LPA stimulates intracellular calcium responses in enteric glia via LPAR1, subsequently recruiting a subpopulation of myenteric neurons; in vivo LPAR1 blockade with AM966 attenuated GI motility and produced enteric neuro- and gliopathy; human CIPO patients showed reduced glial LPAR1 in colon and ileum. LPAR1-specific calcium imaging in enteric glia, in vivo AM966 pharmacological blockade, genetic immunohistochemistry in mice and human CIPO samples, GI motility assay The Journal of clinical investigation High 35166239
2022 LPA1 signaling promotes fibrogenesis and collagen dynamics: BMS-986020 (LPA1 antagonist) potently inhibited LPA1-induced fibrogenesis in a Scar-in-a-Jar in vitro model; in IPF patients, BMS-986020 treatment significantly reduced serum ECM-neoepitope biomarkers correlated with lung function, demonstrating in vitro and clinical antifibrotic mechanism of LPA1 blockade. Scar-in-a-Jar in vitro fibrogenesis assay, serum ECM-neoepitope biomarker analysis in phase 2 IPF trial (NCT01766817), linear mixed models for biomarker-FVC correlation Respiratory research Medium 35303880

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. The Journal of cell biology 628 8922387
2000 Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proceedings of the National Academy of Sciences of the United States of America 417 11087877
1998 A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. Proceedings of the National Academy of Sciences of the United States of America 239 9600933
2004 Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. The Journal of biological chemistry 235 14744855
2007 LPA1 receptor activation promotes renal interstitial fibrosis. Journal of the American Society of Nephrology : JASN 171 18003779
2000 Functional comparisons of the lysophosphatidic acid receptors, LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7 in neuronal cell lines using a retrovirus expression system. Molecular pharmacology 164 11040035
2003 Lysophosphatidic acid (LPA) in malignant ascites stimulates motility of human pancreatic cancer cells through LPA1. The Journal of biological chemistry 154 14660630
1998 Lysophosphatidic acid receptor gene vzg-1/lpA1/edg-2 is expressed by mature oligodendrocytes during myelination in the postnatal murine brain. The Journal of comparative neurology 147 9717712
2013 LPA1-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 136 23322166
2010 Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression. Oncogene 118 21102517
2011 The lysophosphatidic acid receptor LPA1 promotes epithelial cell apoptosis after lung injury. American journal of respiratory cell and molecular biology 114 22021336
2008 Cross-talk between LPA1 and epidermal growth factor receptors mediates up-regulation of sphingosine kinase 1 to promote gastric cancer cell motility and invasion. Cancer research 106 18701480
1998 Edg-2/Vzg-1 couples to the yeast pheromone response pathway selectively in response to lysophosphatidic acid. The Journal of biological chemistry 106 9430689
2003 LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease. Molecular and cellular neurosciences 104 14697676
1999 Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner. Clinical cancer research : an official journal of the American Association for Cancer Research 104 10632375
2006 Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptors. Canadian journal of physiology and pharmacology 95 16902584
2008 Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus. Molecular and cellular neurosciences 94 18708146
2006 GSK-3 is activated by the tyrosine kinase Pyk2 during LPA1-mediated neurite retraction. Molecular biology of the cell 91 16452634
2010 Exploratory, anxiety and spatial memory impairments are dissociated in mice lacking the LPA1 receptor. Neurobiology of learning and memory 73 20388543
2011 A defective ABC transporter of the MRP family, responsible for the bean lpa1 mutation, affects the regulation of the phytic acid pathway, reduces seed myo-inositol and alters ABA sensitivity. The New phytologist 70 21395595
2014 Autotaxin and LPA1 and LPA5 receptors exert disparate functions in tumor cells versus the host tissue microenvironment in melanoma invasion and metastasis. Molecular cancer research : MCR 69 25158955
2011 Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation. Biochemical and biophysical research communications 61 21545790
2003 Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway. Journal of cell science 61 12668728
2013 Lysophosphatidic acid (LPA) and its receptor, LPA1 , influence embryonic schwann cell migration, myelination, and cell-to-axon segregation. Glia 60 24115248
2010 Lysophosphatidic acid receptors LPA1 and LPA3 promote CXCL12-mediated smooth muscle progenitor cell recruitment in neointima formation. Circulation research 60 20360252
2015 The LPA1/ZEB1/miR-21-activation pathway regulates metastasis in basal breast cancer. Oncotarget 59 26098771
2011 Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass. Bone 59 21569876
2011 Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice. PloS one 59 21980482
2007 Lysophosphatidic acid stimulates astrocyte proliferation through LPA1. Neurochemistry international 59 17692995
2007 Lysophosphatidic acid regulates inflammation-related genes in human endothelial cells through LPA1 and LPA3. Biochemical and biophysical research communications 59 17923111
2006 Expression and function of lysophosphatidic acid LPA1 receptor in prostate cancer cells. Endocrinology 56 16809448
2005 Neurochemical changes in LPA1 receptor deficient mice--a putative model of schizophrenia. Neurochemical research 54 16018581
2021 Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD). BMJ open respiratory research 53 34969771
2004 Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist. Bioorganic & medicinal chemistry letters 53 15125924
2014 Lysophosphatidic acid and its receptors LPA1 and LPA3 mediate paclitaxel-induced neuropathic pain in mice. Molecular pain 50 25411045
2013 Lysophosphatidylethanolamine utilizes LPA(1) and CD97 in MDA-MB-231 breast cancer cells. Cellular signalling 49 23838008
2019 Lysophosphatidic acid receptor 1 (LPA1) plays critical roles in microglial activation and brain damage after transient focal cerebral ischemia. Journal of neuroinflammation 45 31429777
2017 Lysophosphatidic acid signaling via LPA1 and LPA3 regulates cellular functions during tumor progression in pancreatic cancer cells. Experimental cell research 45 28189636
2011 Stereotyped fetal brain disorganization is induced by hypoxia and requires lysophosphatidic acid receptor 1 (LPA1) signaling. Proceedings of the National Academy of Sciences of the United States of America 45 21878565
2021 Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis. Oncogene 44 34302117
2019 Modulation of LPA1 receptor-mediated neuronal apoptosis by Saikosaponin-d: A target involved in depression. Neuropharmacology 44 31145906
2025 Efficacy and Safety of Admilparant, an LPA1 Antagonist, in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial. American journal of respiratory and critical care medicine 43 39393084
2019 LPA1 , LPA2 , LPA4 , and LPA6 receptor expression during mouse brain development. Developmental dynamics : an official publication of the American Association of Anatomists 43 30847983
2005 Phosphorylation and desensitization of the lysophosphatidic acid receptor LPA1. The Biochemical journal 42 15369458
1998 Complete cDNA sequence, genomic structure, and chromosomal localization of the LPA receptor gene, lpA1/vzg-1/Gpcr26. Genomics 42 9721207
2020 Microglial lysophosphatidic acid promotes glioblastoma proliferation and migration via LPA1 receptor. Journal of neurochemistry 41 32438456
2014 Lysophosphatidic acid receptor type 1 (LPA1) plays a functional role in osteoclast differentiation and bone resorption activity. The Journal of biological chemistry 41 24429286
2022 LPA1 antagonist BMS-986020 changes collagen dynamics and exerts antifibrotic effects in vitro and in patients with idiopathic pulmonary fibrosis. Respiratory research 40 35303880
2018 LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis. The Journal of investigative dermatology 40 30447238
2000 Vzg-1/lysophosphatidic acid-receptor involved in peripheral pain transmission. Brain research. Molecular brain research 40 10686359
2008 Sharpening the edges of understanding the structure/function of the LPA1 receptor: expression in cancer and mechanisms of regulation. Biochimica et biophysica acta 39 18501205
2012 Opposite roles of LPA1 and LPA3 on cell motile and invasive activities of pancreatic cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 22678979
2021 Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases. Journal of medicinal chemistry 36 34709814
2014 Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex. Brain structure & function 35 25226845
2008 LPA1 is essential for lymphatic vessel development in zebrafish. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 18606866
2006 The role of LPA1 in formation of synapses among cultured hippocampal neurons. Journal of neurochemistry 34 16638019
2018 Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 29477472
2018 Lysophosphatidic acid LPA1 and LPA3 receptors play roles in the maintenance of late tissue plasminogen activator-induced central poststroke pain in mice. Neurobiology of pain (Cambridge, Mass.) 33 31194070
2015 Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3β/β-catenin and PKC/Rho GTPase pathways. Stem cells (Dayton, Ohio) 33 25376707
2015 Antifibrotic effect of lysophosphatidic acid receptors LPA1 and LPA3 antagonist on experimental murine scleroderma induced by bleomycin. Experimental dermatology 33 25959255
2012 The PDZ protein GIPC regulates trafficking of the LPA1 receptor from APPL signaling endosomes and attenuates the cell's response to LPA. PloS one 33 23145131
2006 Rho-dependent, Rho kinase-independent inhibitory regulation of Rac and cell migration by LPA1 receptor in Gi-inactivated CHO cells. Experimental cell research 33 16564043
2002 Immunohistological localization of the myelinating cell-specific receptor LP(A1). Glia 33 11948806
2017 LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy. Neurobiology of pain (Cambridge, Mass.) 31 31194005
2013 Involvement of LPA1 receptor signaling in cerebral ischemia-induced neuropathic pain. Neuroscience 31 23318243
2013 Lysophosphatidic acid stimulates activation of focal adhesion kinase and paxillin and promotes cell motility, via LPA1-3, in human pancreatic cancer. Digestive diseases and sciences 31 24061591
2010 Abnormalities in α/β-CaMKII and related mechanisms suggest synaptic dysfunction in hippocampus of LPA1 receptor knockout mice. The international journal of neuropsychopharmacology 30 20942999
2009 LPA induces IL-6 secretion from aortic smooth muscle cells via an LPA1-regulated, PKC-dependent, and p38alpha-mediated pathway. American journal of physiology. Heart and circulatory physiology 30 20044439
2019 Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR-892b to up-regulate LPAR1 expression. Journal of cellular and molecular medicine 29 31851778
2008 The role of lysophosphatidic acid receptor (LPA1) in the oxygen-induced retinal ganglion cell degeneration. Investigative ophthalmology & visual science 29 18978343
2022 LPA/LPAR1 signaling induces PGAM1 expression via AKT/mTOR/HIF-1α pathway and increases aerobic glycolysis, contributing to keratinocyte proliferation. Life sciences 28 36400203
2019 microRNA-501-5p promotes cell proliferation and migration in gastric cancer by downregulating LPAR1. Journal of cellular biochemistry 28 31746031
2016 ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation. Scientific reports 28 27005960
2008 Involvement of LPA1 receptor signaling in the reorganization of spinal input through Abeta-fibers in mice with partial sciatic nerve injury. Molecular pain 28 18854053
2006 Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA1) in mammalian cells. The Biochemical journal 28 16716145
2021 The Roles of Lpar1 in Central Nervous System Disorders and Diseases. Frontiers in neuroscience 27 34385905
2021 Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway. International journal of molecular sciences 27 34639115
2013 Massively parallel sequencing reveals an accumulation of de novo mutations and an activating mutation of LPAR1 in a patient with metastatic neuroblastoma. PloS one 24 24147068
2013 Lysophosphatidic acid induces vasodilation mediated by LPA1 receptors, phospholipase C, and endothelial nitric oxide synthase. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 24249637
2009 Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cellular signalling 24 19306925
2021 Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance. Cancer research 23 34462276
2014 Identification of heparin-binding EGF-like growth factor (HB-EGF) as a biomarker for lysophosphatidic acid receptor type 1 (LPA1) activation in human breast and prostate cancers. PloS one 23 24828490
2022 LPAR1 regulates enteric nervous system function through glial signaling and contributes to chronic intestinal pseudo-obstruction. The Journal of clinical investigation 22 35166239
2017 LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 28069828
2015 Lysophosphatidylethanolamine increases intracellular Ca(2+) through LPA(1) in PC-12 neuronal cells. Biochemical and biophysical research communications 22 25888792
2015 Phosphorylation and Internalization of Lysophosphatidic Acid Receptors LPA1, LPA2, and LPA3. PloS one 22 26473723
2018 The Hypoxic Tumor Microenvironment Promotes Invadopodia Formation and Metastasis through LPA1 Receptor and EGFR Cooperation. Molecular cancer research : MCR 21 29866927
2018 High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 30317243
2016 LPA1 Mediates Antidepressant-Induced ERK1/2 Signaling and Protection from Oxidative Stress in Glial Cells. The Journal of pharmacology and experimental therapeutics 21 27605627
2015 Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain. Journal of neurochemistry 21 25857358
2015 Both genetic deletion and pharmacological blockade of lysophosphatidic acid LPA1 receptor results in increased alcohol consumption. Neuropharmacology 21 26700247
2003 Lysophosphatidic acid signals through mitogen-activated protein kinase-extracellular signal regulated kinase in ovarian theca cells expressing the LPA1/edg2-receptor: involvement of a nonclassical pathway? Molecular endocrinology (Baltimore, Md.) 21 12730329
2020 Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway. Frontiers in molecular neuroscience 20 32116549
2018 Stress, Depression, Resilience and Ageing: A Role for the LPA-LPA1 Pathway. Current neuropharmacology 20 28699486
2011 LPAR1 and ITGA4 regulate peripheral blood monocyte counts. Human mutation 20 21598361
2007 Lysophosphatidic acid-stimulated interleukin-6 and -8 synthesis through LPA1 receptors on human osteoblasts. Archives of oral biology 19 17915188
2020 Conditional Lpar1 gene targeting identifies cell types mediating neuropathic pain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32929779
2019 Effects of the LPA1 Receptor Deficiency and Stress on the Hippocampal LPA Species in Mice. Frontiers in molecular neuroscience 18 31244601
2018 Lysophosphatidic acid and its receptor LPA1 mediate carrageenan induced inflammatory pain in mice. European journal of pharmacology 18 30321532
2015 Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension. Hypertension (Dallas, Tex. : 1979) 18 26123684

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