Affinage

PTGDS

Prostaglandin-H2 D-isomerase · UniProt P41222

Length
190 aa
Mass
21.0 kDa
Annotated
2026-06-10
51 papers in source corpus 21 papers cited in narrative 21 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

PTGDS (L-PGDS) is a bifunctional lipocalin that couples enzymatic prostaglandin D2 (PGD2) synthesis to a structurally independent hydrophobic-ligand carrier activity, allowing it to regulate inflammation, vascular barrier integrity, metabolism, and cell fate across multiple tissues (PMID:34615734). Its two functions are genetically separable: in acute lung injury, the PGD2-synthesizing activity restrains pulmonary edema while the lipocalin carrier function—independent of PGD2 production—limits mucin formation and inflammatory-cell infiltration (PMID:34615734, PMID:30734298). PGD2 generated by L-PGDS signals through the DP1 prostanoid receptor to drive ERK-dependent neuroprotection (PMID:25474649) and CD36+ phagocyte conversion in ischemic brain (PMID:39451255), and through nuclear PPARγ to promote ANP secretion in cardiac atria within HIF-1α– and ET-1/COX2-initiated cascades (PMID:29287795, PMID:31541683). The downstream PGD2 metabolite 15d-PGJ2, produced intracellularly, covalently lipoxidates CaMKII at Cys495 to dampen CaMKII oligomerization and protect cardiomyocytes from ischemia/reperfusion injury (PMID:40396239). Beyond lipid signaling, L-PGDS acts as a molecular chaperone/disaggregase that directly binds monomeric Aβ via its C-terminus and disassembles preformed fibrils (PMID:31467325), and it physically engages HMOX1 to control heme catabolism, intracellular iron, and ferroptosis (PMID:39706989), consistent with disrupted iron homeostasis in knockout mice (PMID:41274340). In cancer, PTGDS interacts with MYH9 to activate Wnt–β-catenin–STAT3 signaling and drive DLBCL tumorigenesis, with N-glycosylation at Asn51/Asn78 governing its nuclear translocation and stability (PMID:34743203), whereas YAP and the CUL4B/PRC2 complex act as upstream repressors of its expression (PMID:32851567, PMID:26025376). PKC phosphorylation activates L-PGDS to suppress PI3-K/Akt signaling and trigger Bad-dependent apoptosis (PMID:12388064).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2002 High

    Established that L-PGDS is not merely a constitutive synthase but a signal-responsive enzyme whose PKC phosphorylation links it to pro-apoptotic suppression of the PI3-K/Akt survival pathway.

    Evidence In vitro PKC phosphorylation of recombinant L-PGDS with antisense depletion, PI3-K activity assays, and caspase-3 readouts in cells

    PMID:12388064

    Open questions at the time
    • Phosphosite(s) on L-PGDS not mapped
    • Direct mechanism by which L-PGDS inhibits PI3-K (enzymatic product vs. protein interaction) unresolved
  2. 2009 Low

    Tested whether extracellular L-PGDS has direct cellular effects, showing it inhibits astrocyte proliferation and mitochondrial ATP production at pathological concentrations.

    Evidence Recombinant L-PGDS added to astrocyte cultures with proliferation and ATP assays

    PMID:19598000

    Open questions at the time
    • Single in vitro functional assay with no pathway delineation
    • Receptor or uptake mechanism unknown
    • Enzymatic vs. lipocalin contribution not distinguished
  3. 2012 Medium

    Placed PTGDS/PGD2 signaling as a novel regulator of testicular descent, distinct from the androgen pathway.

    Evidence Ptgds knockout mice with cryptorchidism phenotyping and Rxfp2 expression analysis

    PMID:23076868

    Open questions at the time
    • Receptor mediating the descent phenotype not identified
    • Mechanistic link between PGD2 and Rxfp2 expression unresolved
  4. 2014 Medium

    Defined a linear L-PGDS–PGD2–DP1–pERK axis as the effector of dexamethasone neuroprotection, demonstrating receptor-coupled downstream signaling of the synthase product.

    Evidence Intracerebroventricular inhibitor epistasis (L-PGDS, DP1, MAPK) in a neonatal rat hypoxic-ischemic model

    PMID:25474649

    Open questions at the time
    • Cell types producing vs. responding to PGD2 not separated
    • Direct vs. indirect DP1–ERK coupling not biochemically shown
  5. 2015 High

    Identified upstream epigenetic control, showing CUL4B/PRC2 transcriptionally represses Ptgds and that its enzymatic activity drives astrocyte fate in neural progenitors.

    Evidence Cul4b knockout mice, ChIP at the Ptgds locus, AT56 inhibition, shRNA knockdown, and gain-of-function rescue in NPC cultures

    PMID:26025376

    Open questions at the time
    • PGD2 receptor mediating gliogenesis not identified
    • Direct PRC2 mark deposition vs. CUL4B-mediated effects not fully separated
  6. 2017 Medium

    Showed hypoxia couples HIF-1α induction of L-PGDS to PPARγ-dependent ANP secretion, establishing an intracellular nuclear-receptor route for PGD2 signaling in the heart.

    Evidence Sequential pharmacological inhibitor epistasis in isolated perfused beating rat atria

    PMID:29287795

    Open questions at the time
    • Direct PGD2–PPARγ binding in this system not demonstrated
    • Ex vivo single-lab pharmacology only
  7. 2019 Medium

    Extended the cardiac axis upstream to ET-1/COX2 and revealed an NRF2-mediated positive feedback loop sustaining L-PGDS expression.

    Evidence ET receptor antagonists and pathway western blots in beating rat atria

    PMID:31541683

    Open questions at the time
    • NRF2 regulation of L-PGDS not shown at promoter level
    • Single method type, single lab
  8. 2019 High

    Resolved a non-enzymatic chaperone function, showing L-PGDS directly binds and disaggregates Aβ via its lipocalin cavity.

    Evidence NMR, SAXS, TEM, and thioflavin-T assays defining the L-PGDS–Aβ40 binding mode and disaggregase activity

    PMID:31467325

    Open questions at the time
    • In vivo relevance to amyloid pathology not established
    • Stoichiometry and turnover of disaggregation unresolved
  9. 2019 High

    Demonstrated cell-stage-specific metabolic roles, with premature-adipocyte L-PGDS-derived PGD2 driving obesity and insulin resistance.

    Evidence Two adipose-specific conditional knockout models (aP2-Cre, AdipoQ-Cre) under high-fat diet with metabolic phenotyping

    PMID:30760783

    Open questions at the time
    • Receptor mediating the adipocyte phenotype not pinned down
    • Mechanism of stage specificity unresolved
  10. 2019 Medium

    Connected L-PGDS to glucocorticoid-induced leptin expression and identified it as the off-target of CB2 ligands suppressing leptin.

    Evidence Pharmacological screening, CB2-KO adipocytes, docking, and inhibitor experiments in differentiated preadipocytes

    PMID:31129049

    Open questions at the time
    • Direct binding of CB2 ligands to L-PGDS not crystallographically confirmed
    • Mechanism linking L-PGDS to leptin transcription unknown
  11. 2019 High

    Showed PGD2 from non-hematopoietic L-PGDS protects the endothelial barrier in acute lung injury via the DP receptor.

    Evidence L-PGDS KO mice, bone marrow chimeras, Miles permeability assay, and DP agonist barrier assays in the HCl ALI model

    PMID:30734298

    Open questions at the time
    • Endothelial DP1 vs. DP2 contribution not separated
    • Downstream barrier-stabilizing effectors unidentified
  12. 2020 Medium

    Identified YAP as an upstream repressor of L-PGDS in gastric cancer, with L-PGDS opposing YAP-driven stemness.

    Evidence Reciprocal YAP/L-PGDS gain- and loss-of-function with sphere formation and xenograft rescue

    PMID:32851567

    Open questions at the time
    • Direct vs. indirect YAP repression of the locus not resolved
    • Enzymatic vs. lipocalin basis of tumor suppression unclear
  13. 2021 High

    Genetically separated the enzymatic and lipocalin functions of L-PGDS in lung injury using PGD2-null/lipocalin-intact point-mutant mice.

    Evidence L-PGDS-deficient vs. point-mutant mice with edema, BALF, and mucin readouts in the HCl ALI model

    PMID:34615734

    Open questions at the time
    • Ligand(s) carried by the lipocalin function in lung not identified
    • Receptor/effector for the lipocalin-mediated anti-inflammatory effect unknown
  14. 2021 High

    Revealed a nuclear, interaction-based oncogenic role, with PTGDS binding MYH9 to activate Wnt–β-catenin–STAT3 signaling, regulated by N-glycosylation.

    Evidence Co-IP mass spectrometry, glycosylation-site mutagenesis (Asn51/Asn78), knockdown/rescue, and xenografts in DLBCL

    PMID:34743203

    Open questions at the time
    • Whether MYH9 binding requires enzymatic activity unknown
    • Mechanism coupling glycosylation to nuclear import unresolved
  15. 2024 High

    Established a physical PTGDS–HMOX1 interaction controlling heme catabolism, iron levels, and ferroptosis in lymphoma cells.

    Evidence Co-IP/TMT-MS, HMOX1 H25A interaction-site mutation, ferroptosis and iron assays, and xenografts

    PMID:39706989

    Open questions at the time
    • Whether PTGDS modulates HMOX1 catalysis directly or via cofactor delivery unresolved
    • Role of PGD2 vs. lipocalin function in this interaction unclear
  16. 2024 Medium

    Extended the PGD2–DP1 axis to post-stroke immunity, showing it converts microglia/macrophages to a CD36+ phagocytic scavenger phenotype.

    Evidence Mouse stroke model immunohistochemistry plus ex vivo PGD2 treatment and phagocytosis assays

    PMID:39451255

    Open questions at the time
    • DP1 signaling pathway driving CD36 induction not delineated
    • In vivo causality from genetic loss not shown
  17. 2025 High

    Defined the intracellular mechanism of cardiac protection: L-PGDS-derived 15d-PGJ2 covalently lipoxidates CaMKII-Cys495 to limit its oligomerization and overactivation.

    Evidence Biotin-15d-PGJ2 chemical proteomics with LC-MS/MS site mapping, L-PGDS OE/KD across cardiomyocyte models, and a mouse I/R model

    PMID:40396239

    Open questions at the time
    • In vivo contribution of Cys495 modification vs. other targets not isolated
    • Regulation of intracellular 15d-PGJ2 levels by L-PGDS not quantified
  18. 2025 Medium

    Supported a systemic role in iron recycling, with L-PGDS knockout mice showing disrupted iron distribution and reduced free heme consistent with impaired heme catabolism.

    Evidence L-PGDS KO mice with plasma/tissue iron quantification, RBC morphology, and NRF2/FPN/Hmox1 expression

    PMID:41274340

    Open questions at the time
    • No direct biochemical reconstitution of porphyrin binding
    • Causal link between porphyrin buffering and iron phenotype inferential
  19. 2025 Medium

    Implicated PTGDS in fibroinflammation, showing fibroblast PTGDS recruits Th2 cells and promotes skin fibrosis, reversible by enzymatic inhibition.

    Evidence PTGDS overexpression in fibroblasts, AT56 inhibition, T-cell migration assays, and a bleomycin skin fibrosis model

    PMID:40478772

    Open questions at the time
    • Receptor mediating Th2 chemotaxis not identified
    • Chemokines downstream of PGD2 not mechanistically validated
  20. 2025 Medium

    Linked exosomal PTGDS to brain aging, showing PTGDS-bearing exosomes drive DP1-dependent microglial senescence and cognitive decline.

    Evidence Brain-derived exosome transfer, PTGDS knockdown, and DP1 antagonism with senescence and cognitive readouts in aged mice

    PMID:40974022

    Open questions at the time
    • Mechanism of PTGDS exosomal loading unknown
    • DP1 downstream senescence program not defined
  21. 2025 Medium

    Characterized regulation of L-PGDS under hepatic insulin resistance, showing transcriptional downregulation with cytoplasm-to-nucleus trafficking, excluding proteasomal/autophagic/ubiquitin routes.

    Evidence HepG2 palmitate/insulin model with inhibitor panels, ubiquitination Co-IP, and subcellular fractionation

    PMID:41386368

    Open questions at the time
    • Transcription factor driving downregulation not identified
    • Functional consequence of nuclear trafficking in hepatocytes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How L-PGDS coordinates its enzymatic PGD2/15d-PGJ2 output with its ligand-carrier and protein-interaction functions across tissues, and which receptors or partners dominate in each context, remains unresolved.
  • No unified structural model coupling catalytic and lipocalin/binding functions
  • Tissue-specific receptor preference (DP1 vs DP2 vs PPARγ) not systematically defined
  • Endogenous porphyrin/hydrophobic ligands of the carrier function only partially identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0016491 oxidoreductase activity 3 GO:0044183 protein folding chaperone 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 2 GO:0005634 nucleus 2 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2
Partners
CAMKIIHMOX1MYH9

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 L-PGDS is phosphorylated and enzymatically activated by PKC in response to phorbol ester (PMA). Activated L-PGDS inhibits PI3-K activity, leading to reduced PKB/Akt phosphorylation, hypophosphorylation and activation of Bad, and subsequent caspase-3 activation and apoptosis. Antisense depletion of L-PGDS prevented PI3-K inactivation, caspase-3 activation, and apoptosis. In vitro PKC phosphorylation of recombinant L-PGDS; antisense RNA depletion; PI3-K activity assay; western blot for Akt, Bad, Rb phosphorylation; caspase-3 activation assay American journal of physiology. Cell physiology High 12388064
2019 L-PGDS acts as a molecular chaperone/disaggregase: it directly binds monomeric Aβ40 and Aβ(25-35) via the Aβ C-terminus (N-terminus remains free), inhibiting spontaneous aggregation, and also disassembles pre-formed Aβ fibrils. The binding mode was resolved by NMR spectroscopy and SAXS, yielding a structural model of the L-PGDS–Aβ40 complex. NMR spectroscopy (binding mode), SAXS (solution structure), TEM (fibril morphology), thioflavin-T aggregation assay, proteomics on AD brain insoluble fractions Scientific reports High 31467325
2014 Dexamethasone upregulates L-PGDS expression and PGD2 biosynthesis in neonatal rat brain; the neuroprotective effect of dexamethasone against hypoxic-ischemic injury requires the L-PGDS–PGD2–DP1–pERK signaling axis, as pharmacological inhibition of L-PGDS (SeCl4), DP1 (MK-0524), or MAPK (PD98059) each abolished dexamethasone-induced pERK-44 elevation and neuroprotection. Intracerebroventricular drug injections; western blot for L-PGDS, DP1, pERK1/2; ELISA for PGD2; pharmacological inhibitor epistasis; neonatal rat HI model PloS one Medium 25474649
2015 CUL4B/PRC2 complex transcriptionally represses Ptgds expression in neural progenitor cells (NPCs). Loss of Cul4b increases PTGDS levels, promoting conversion of NPCs to GFAP+ astrocytes; this phenotype is rescued by pharmacological inhibition of PTGDS enzymatic activity (AT56) or shRNA-mediated Ptgds knockdown, and is phenocopied by exogenous PTGDS addition to wild-type NPCs. Cul4b knockout mouse model; NPC culture; GFAP/S100β immunostaining; AT56 inhibitor; shRNA knockdown; exogenous PTGDS addition; ChIP for CUL4B/PRC2 at Ptgds locus Human molecular genetics High 26025376
2019 L-PGDS-derived PGD2, produced specifically in premature (but not mature) adipocytes, promotes obesity and insulin resistance under high-fat diet conditions. Deletion of L-PGDS in premature adipocytes (aP2-Cre) reduced PGD2 production in WAT, decreased body weight gain, adipocyte size, and serum lipids, and improved insulin sensitivity, with altered expression of adipogenic, lipogenic, and macrophage marker genes. Adipose-specific conditional knockout mice (aP2-Cre and AdipoQ-Cre); HFD feeding; PGD2 ELISA; glucose/insulin tolerance tests; gene expression profiling Scientific reports High 30760783
2019 L-PGDS-derived PGD2 protects against acute lung injury by enhancing endothelial barrier function via the DP (D prostanoid) receptor. In HCl-induced ALI, inflamed endothelial/epithelial cells express L-PGDS; L-PGDS-deficient mice show exacerbated vascular permeability that is suppressed by DP receptor agonism. Hematopoietic reconstitution with WT bone marrow did not rescue the edema phenotype, confirming non-hematopoietic origin. L-PGDS KO mice; HCl intratracheal model; Miles assay for vascular permeability; immunostaining; bone marrow reconstitution; in vitro endothelial barrier assay with DP agonist The Journal of pathology High 30734298
2021 L-PGDS has two mechanistically distinct protective roles in acute lung injury: (1) its PGD2-synthesizing enzymatic activity inhibits pulmonary edema formation, and (2) its lipocalin carrier function (independent of PGD2 production) decreases mucin formation and inflammatory cell infiltration, as dissected using point-mutant mice that lack PGD2 producibility but retain lipocalin ability. L-PGDS-deficient mice vs. L-PGDS point-mutant (PGD2-null, lipocalin-intact) mice; HCl intratracheal model; lung water content; BALF protein and leukocyte counts; mucin staining; IL-33 mRNA measurement Journal of immunology High 34615734
2021 PTGDS interacts with MYH9 (identified by co-immunoprecipitation–mass spectrometry). PTGDS promotes DLBCL tumorigenesis through MYH9-mediated activation of the Wnt–β-catenin–STAT3 pathway by influencing ubiquitination and degradation of GSK3-β. N-glycosylation of PTGDS at Asn51 and Asn78 regulates its nuclear translocation, protein half-life, and proliferative activity. Co-IP mass spectrometry; site-directed mutagenesis of glycosylation sites (Asn51, Asn78); lentiviral KD; rescue experiments; subcellular fractionation; western blot for Wnt/β-catenin/STAT3 pathway; in vitro and xenograft models Cell death and differentiation High 34743203
2017 Hypoxia activates HIF-1α, which upregulates L-PGDS expression in beating rat atria; L-PGDS-derived PGD2 then activates PPARγ to promote ANP secretion. The HIF-1α–L-PGDS–PPARγ signaling axis was established by sequential pharmacological inhibition (2-methoxyestradiol for HIF-1α; AT-56/HQL-49 for L-PGDS; GW9662 for PPARγ). Isolated perfused beating rat atria; pharmacological inhibitors (2-methoxyestradiol, AT-56, HQL-49, GW9662); western blot for HIF-1α, L-PGDS, PPARγ; ANP secretion measurement Prostaglandins & other lipid mediators Medium 29287795
2019 Endogenous ET-1 (induced by hypoxia) promotes ANP secretion via COX2–L-PGDS–PPARγ signaling. L-PGDS-derived PGD2 also feeds back to regulate L-PGDS expression through an NRF2-mediated positive feedback mechanism in beating rat atria. Isolated perfused beating rat atria; ET receptor antagonists; western blot for COX2, L-PGDS, PPARγ, NRF2; PGD2 ELISA; ANP secretion measurement Peptides Medium 31541683
2019 L-PGDS mediates glucocorticoid-induced leptin expression in differentiated adipocytes: glucocorticoids induce L-PGDS, which in turn positively regulates leptin. Aldosterone, while also inducing both L-PGDS and leptin, does not require L-PGDS for leptin induction. Target deconvolution and docking identified L-PGDS as the off-target responsible for leptin suppression by CB2 ligands AM630 and WIN55212-2. Pharmacological screening; genetic (CB2-KO) adipocytes; docking simulation; L-PGDS inhibitor (AM630/WIN55212-2); gene/protein expression in differentiated primary preadipocytes Biochemical pharmacology Medium 31129049
2020 In gastric cancer cells, YAP directly suppresses L-PTGDS (L-PGDS) expression; overexpression of L-PGDS reverses YAP-induced stemness promotion, inhibits proliferation and self-renewal in vitro, and reverses the pro-tumor effect of YAP in vivo, establishing YAP as an upstream negative regulator of L-PGDS. Gain- and loss-of-function (YAP OE/KD); L-PGDS/PTGDR2 OE; sphere formation; xenograft tumor model; RT-PCR; western blot; IHC International journal of clinical oncology Medium 32851567
2024 PTGDS physically interacts with the heme-degrading enzyme HMOX1 (identified by TMT-mass spectrometry). PTGDS knockdown increases intracellular iron and induces ferroptosis in peripheral T cell lymphoma cells by promoting HMOX1-mediated heme catabolism and ferritin autophagy. An H25A point mutation in HMOX1 identified the specific catalytic site required for this interaction. Co-IP/TMT-mass spectrometry; lentiviral KD; HMOX1 H25A point mutation; ferroptosis assays; iron level measurement; xenograft model; RNA-sequencing British journal of cancer High 39706989
2025 Intracellular L-PGDS-derived 15d-PGJ2 covalently modifies (lipoxidation) CaMKII at cysteine 495 (CaMKII-δ9), dampening CaMKII oligomer formation and overactivation, thereby alleviating cardiomyocyte death and cardiac ischemia/reperfusion injury. L-PGDS is downregulated in I/R-injured cardiac tissue; its overexpression mitigates injury while knockdown exacerbates it. Biotin-tagged 15d-PGJ2 analog + LC-MS/MS (target ID); L-PGDS OE/KD in neonatal and adult cardiomyocytes and hESC-derived cardiomyocytes; mouse I/R model; CaMKII oligomer assays; transcriptome profiling Circulation High 40396239
2025 L-PGDS knockout mice display disrupted iron homeostasis: elevated plasma iron, increased splenic iron, reduced hepatic iron, decreased plasma free heme/hemin, and modest RBC enlargement, consistent with impaired heme catabolism. Transcript-protein mismatches in NRF2 and ferroportin (FPN) indicate redox imbalance. These findings support a model in which L-PGDS buffers porphyrin intermediates during heme catabolism, functioning as an auxiliary factor in iron recycling. L-PGDS KO mice; plasma/tissue iron quantification; RBC morphology; western blot and qPCR for NRF2, FPN, Hmox1; splenic/hepatic iron histochemistry Prostaglandins & other lipid mediators Medium 41274340
2025 PTGDS-overexpressed skin fibroblasts upregulate chemokines and enhance migration of CD4+ T cells, particularly Th2 cells; this is reversed by the PTGDS inhibitor AT56. In a bleomycin-induced skin fibrosis model, PTGDS overexpression promotes Th2 infiltration and fibrosis, while AT56 attenuates inflammation and fibrosis in vivo. PTGDS OE in BJ fibroblasts; AT56 inhibitor; CD4+ T cell migration assay; Th2 subset analysis; bleomycin mouse model; IHC for fibrosis markers Rheumatology (Oxford, England) Medium 40478772
2024 The L-PGDS–PGD2–DP1 (but not DP2) axis regulates phagocytosis by CD36+ microglia/macrophages in ischemic areas after stroke. L-PGDS is upregulated in the leptomeninges of ischemic areas; DP1 is highly expressed on CD36+ MGs/MΦs uniquely present within ischemic areas; PGD2 treatment promotes conversion of MGs/MΦs into CD36+ scavenger phenotype and increases their phagocytic activity. Mouse ischemic stroke model; immunohistochemistry for L-PGDS, PGD2, DP1, DP2, CD36; PGD2 treatment of MGs/MΦs; phagocytosis assay Cells Medium 39451255
2025 PTGDS in brain-derived exosomes from aged mice activates DP1 receptor signaling (via elevated PGD2), promoting microglial overactivation, lipid droplet accumulation, senescence-associated secretory phenotype secretion, myeloid cell infiltration, and cognitive decline. Blocking DP1 receptor ameliorates exosome-induced microglial senescence and cognitive decline in vivo. Brain-derived exosome transfer to young mice; PTGDS knockdown in exosomes; DP1 receptor antagonist; microglial senescence assays (SASP, lipid droplets); cognitive testing; aged mouse model Aging cell Medium 40974022
2025 Insulin resistance in HepG2 cells downregulates L-PGDS at the transcriptional level (decreased mRNA and protein), and induces trafficking of L-PGDS from the cytoplasm to the nucleus. Proteasomal degradation, autophagy, and ubiquitination pathways were experimentally excluded as mechanisms of downregulation. HepG2 palmitate/insulin model; MG132 (proteasome inhibitor), chloroquine (autophagy inhibitor), cycloheximide (translation inhibitor); co-immunoprecipitation for ubiquitination; subcellular fractionation; qRT-PCR; western blot Prostaglandins & other lipid mediators Medium 41386368
2009 L-PGDS (at concentrations found in patients with intracranial hypertension or normal-tension glaucoma) directly inhibits astrocyte proliferation and mitochondrial ATP production in vitro. Recombinant L-PGDS added to astrocyte cultures; cell proliferation assay; mitochondrial ATP production measurement Journal of molecular neuroscience Low 19598000
2012 Heterozygous and homozygous Ptgds-knockout mice display unilateral cryptorchidism (affecting inguinoscrotal phase of testicular descent) at rates of 16% and 24%, respectively, associated with decreased Rxfp2 mRNA in the gubernaculum but no impairment of the androgen pathway, identifying PTGDS/PGD2 signaling as a novel component of testicular descent regulation. Ptgds KO mouse model; histology; immunohistochemistry; qPCR for Rxfp2 and androgen pathway genes; gubernaculum morphology Human mutation Medium 23076868

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Glycoprotein PTGDS promotes tumorigenesis of diffuse large B-cell lymphoma by MYH9-mediated regulation of Wnt-β-catenin-STAT3 signaling. Cell death and differentiation 88 34743203
2008 Knockout of the l-pgds gene aggravates obesity and atherosclerosis in mice. Biochemical and biophysical research communications 46 19070593
2022 MSC-Derived Extracellular Vesicle-Delivered L-PGDS Inhibit Gastric Cancer Progression by Suppressing Cancer Cell Stemness and STAT3 Phosphorylation. Stem cells international 35 35087591
2014 Dexamethasone protects neonatal hypoxic-ischemic brain injury via L-PGDS-dependent PGD2-DP1-pERK signaling pathway. PloS one 34 25474649
2019 Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fibrils. Scientific reports 31 31467325
2016 L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response. Neurochemical research 31 27900597
2009 L-PGDS (betatrace protein) inhibits astrocyte proliferation and mitochondrial ATP production in vitro. Journal of molecular neuroscience : MN 30 19598000
2002 Elevated L-PGDS activity contributes to PMA-induced apoptosis concomitant with downregulation of PI3-K. American journal of physiology. Cell physiology 27 12388064
2019 Role of the L-PGDS-PGD2-DP1 receptor axis in sleep regulation and neurologic outcomes. Sleep 25 30893431
2017 Relationship between HSP90a, NPC2 and L-PGDS proteins to boar semen freezability. Journal of animal science and biotechnology 25 28270911
2012 Unilateral cryptorchidism in mice mutant for Ptgds. Human mutation 24 23076868
2014 Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid-cycling bipolar disorder patients compared with healthy control subjects. The international journal of neuropsychopharmacology 23 25522430
2023 Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons. Scientific reports 21 36949072
2012 Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit-hyperactivity disorder and bipolar disorder. Journal of affective disorders 21 22370065
2015 Lack of CUL4B leads to increased abundance of GFAP-positive cells that is mediated by PTGDS in mouse brain. Human molecular genetics 20 26025376
2023 The tertiary lymphoid structure-related signature identified PTGDS in regulating PD-L1 and promoting the proliferation and migration of glioblastoma. Heliyon 19 38205335
2020 The prostaglandin synthases, COX-2 and L-PGDS, mediate prostate hyperplasia induced by low-dose bisphenol A. Scientific reports 18 32753632
2021 Protectin DX promotes the inflammatory resolution via activating COX-2/L-PGDS-PGD2 and DP1 receptor in acute respiratory distress syndrome. International immunopharmacology 17 34920958
2019 L-PGDS-produced PGD2 in premature, but not in mature, adipocytes increases obesity and insulin resistance. Scientific reports 15 30760783
2020 YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2. International journal of clinical oncology 14 32851567
2019 L-PGDS-derived PGD2 attenuates acute lung injury by enhancing endothelial barrier formation. The Journal of pathology 14 30734298
2024 Targeting PTGDS Promotes ferroptosis in peripheral T cell lymphoma through regulating HMOX1-mediated iron metabolism. British journal of cancer 13 39706989
2020 Dexamethasone Suppresses Radicular Pain Through Targeting the L-PGDS/PI3K/Akt Pathway in Rats With Lumbar Disc Herniation. Pain practice : the official journal of World Institute of Pain 11 32640501
2025 Intracellular L-PGDS-Derived 15d-PGJ2 Inhibits CaMKII Through Lipoxidation to Alleviate Cardiac Ischemia/Reperfusion Injury. Circulation 10 40396239
2020 L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis. Aging 10 33361529
2014 18F-glutathione conjugate as a PET tracer for imaging tumors that overexpress L-PGDS enzyme. PloS one 10 25111383
2025 Pan cancer research reveals the role of PTGDS in tumor suppression and immune regulation. NPJ precision oncology 9 41028158
2022 Oral exposure to DEHP may stimulate prostatic hyperplasia associated with upregulation of COX-2 and L-PGDS expressions in male adult rats. Reproductive toxicology (Elmsford, N.Y.) 9 35905844
2019 Endogenous ET-1 promotes ANP secretion through activation of COX2-L-PGDS-PPARγ signaling in hypoxic beating rat atria. Peptides 9 31541683
2015 Role of Lipocalin-type prostaglandin D2 synthase (L-PGDS) and its metabolite, prostaglandin D2, in preterm birth. Prostaglandins & other lipid mediators 7 25964109
2014 Lipocalin-like prostaglandin D synthase (L-PGDS) concentration in aqueous humour in patients with open-angle glaucoma. Journal of glaucoma 7 23059482
2019 A structure-function approach identifies L-PGDS as a mediator responsible for glucocorticoid-induced leptin expression in adipocytes. Biochemical pharmacology 6 31129049
2017 HIF-1α-l-PGDS-PPARγ regulates hypoxia-induced ANP secretion in beating rat atria. Prostaglandins & other lipid mediators 6 29287795
2025 Targeting PTGDS inhibits pro-inflammatory fibroblasts associated with skin fibrosis in systemic sclerosis. Rheumatology (Oxford, England) 5 40478772
2024 L-PGDS-PGD2-DP1 Axis Regulates Phagocytosis by CD36+ MGs/MΦs That Are Exclusively Present Within Ischemic Areas After Stroke. Cells 5 39451255
2019 ER-depletion lowering the 'hypothalamus-uterus-kidney' axis functions by perturbing the renal ERβ/Ptgds signalling pathway. Aging 5 31708494
2025 PTGDS deficiency as a driver of M2 macrophage polarization and immunosuppressive microenvironment in esophageal squamous cell carcinoma: an experimental study. International journal of surgery (London, England) 3 40497781
2025 DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains. Aging cell 3 40974022
2024 Leveraging cell death patterns to predict metastasis in prostate adenocarcinoma and targeting PTGDS for tumor suppression. Scientific reports 2 39289451
2024 The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption. Cells 2 39682755
2021 L-PGDS Attenuates Acute Lung Injury by Prostaglandin D2 in Both Dependent and Independent Ways. Journal of immunology (Baltimore, Md. : 1950) 2 34615734
2004 [PGD(2)/L-PGDS system in hypertension and renal injury]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica 2 14695455
2025 Melatonin modulated GPX5 and PTGDS expression in Bactrian camel epididymis mainly via receptor MT1†. Biology of reproduction 1 39951496
2025 Ptgds downregulation protect vestibular hair cells from aminoglycoside-induced vestibulotoxicity. PloS one 1 40198625
2026 ALB, GPX5 and PTGDS as potential biomarkers for the aging processes of the dog epididymis. Reproduction, fertility, and development 0 41433920
2026 PTGDS is a potential marker for lung adenocarcinoma identified in a pancancer analysis. Scientific reports 0 41651923
2026 Low PTGDS Expression Facilitates HNSCC by Suppressing Programmed Cell Death and Reducing B Cell-Mediated Immune Responses. Mediators of inflammation 0 41866775
2026 Targeting Circadian Rhythm Disruption in Glaucoma: PTGDS Mediates Trabecular Meshwork Fibrosis and Is Therapeutically Targeted by Aprepitant. Translational vision science & technology 0 42065486
2025 PTGDS: As a Specific Biomarker for Septic Cardiomyopathy. Infection and drug resistance 0 41180608
2025 Lipocalin-type prostaglandin D₂ synthase (L-PGDS) deficiency disrupts heme catabolism and iron homeostasis in mice. Prostaglandins & other lipid mediators 0 41274340
2025 Revealing the biochemical regulations of L-PGDS in hepatic insulin-resistance using HepG2 cells. Prostaglandins & other lipid mediators 0 41386368

Missed literature

Know a paper Affinage missed for PTGDS? Flag it for the maintainers and the community.

No submissions yet.