Affinage

HAPLN1

Hyaluronan and proteoglycan link protein 1 · UniProt P10915

Length
354 aa
Mass
40.2 kDa
Annotated
2026-06-10
48 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HAPLN1 is a secreted extracellular matrix link protein that non-covalently stabilizes the association between hyaluronan (HA) and proteoglycans, organizing the pericellular and interstitial matrix across cartilage, heart, brain, and tumor microenvironments (PMID:17822691, PMID:33064036). It is required for versican stability during cardiac development, and its loss produces atrioventricular septal and myocardial defects (PMID:17822691). The same HA-scaffolding activity underlies organized ECM architecture in the nervous system: HAPLN1 drives condensation of chondroitin sulfate proteoglycans into perineuronal nets that consolidate fear memories, and live-imaging probes reveal that it templates developmentally regulated HA-scaffolded ECM around neurons (PMID:37022587, PMID:39251350). In tissue mechanics and morphogenesis it contributes, with lumican and collagen I, to HA-dependent stiffening and folding of the developing human neocortex via CD168 and ERK signaling, and in regenerating zebrafish heart and spinal cord hapln1-expressing cells deposit HA to support progenitor and cardiomyocyte proliferation through CD44 signaling (PMID:30078576, PMID:35652354, PMID:41959443). Functional activity maps to specific domains: the SP-IgV (Ig-like) domain confers pro-tumorigenic properties, and the proteoglycan tandem repeat 1 (PTR1) domain induces survival gene expression (PMID:19351750, PMID:36480501). HAPLN1 expression is transcriptionally induced in granulosa cells by LH via RUNX1/RUNX2 binding at its promoter and by FSH/IGF-I through PI3K/Akt signaling, where it promotes cell survival (PMID:20339004, PMID:12586755). In aging and cancer, declining matrix HAPLN1 raises endothelial and lymphatic permeability through a HA-dependent cascade that lowers ICAM1 and stabilizes VE-cadherin junctions, while in tumors it drives invasion and metastasis through TGF-β/SMAD signaling, TNFR2/TNF/HA-mediated EMT, and versican-GDF11 trapping that activates SMAD2/3 (PMID:30279172, PMID:38472454, PMID:34724589, PMID:37095087, PMID:38618242). In multiple myeloma, stroma-derived HAPLN1 engages a cell-surface CH60–TLR4 complex to activate an atypical, bortezomib-resistant NF-κB pathway, and a HAPLN1-derived matrikine signals through NF-κB–IFN-β–STAT1 to promote bone marrow homing and drug resistance (PMID:29279332, PMID:36625202, PMID:37647592).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 Medium

    Established that HAPLN1 is a regulated gene product downstream of gonadotropin signaling, answering how hormonal cues control its production in the ovary.

    Evidence Pharmacological PI3K and p38 inhibition in primary rat granulosa cells treated with FSH and IGF-I

    PMID:12586755

    Open questions at the time
    • Transcription factors mediating induction not identified here
    • Functional consequence in ovary not addressed
  2. 2007 High

    Defined the core structural function of HAPLN1 by showing it stabilizes the HA-versican interaction and is required for normal cardiac morphogenesis.

    Evidence Crtl1-/- knockout mouse with immunohistochemistry and versican expression analysis

    PMID:17822691

    Open questions at the time
    • Molecular basis of versican destabilization not resolved
    • Whether the cardiac role generalizes to other organs untested here
  3. 2009 Medium

    Localized pro-tumorigenic activity to a discrete protein module, showing the SP-IgV domain is sufficient for transformed-cell behavior.

    Evidence Domain construct transfection into mesothelioma cells with proliferation, motility, invasion, and soft-agar assays

    PMID:19351750

    Open questions at the time
    • Receptor or binding partner for the IgV domain not identified
    • Single cell-type, single lab
  4. 2010 High

    Identified the direct transcriptional control of HAPLN1, showing RUNX1/2 bind its promoter to drive LH-induced expression and granulosa cell survival.

    Evidence ChIP, luciferase reporter with RUNX-site mutation, RUNX siRNA and dominant-negative constructs in rat granulosa cells

    PMID:20339004

    Open questions at the time
    • Downstream survival effectors of HAPLN1 not defined
    • Relevance beyond ovarian follicle untested
  5. 2017 Medium

    Revealed an unexpected signaling role for stroma-derived HAPLN1, showing it activates a proteasome-inhibitor-resistant atypical NF-κB pathway driving myeloma drug resistance.

    Evidence HAPLN1 protein treatment of MM cells with NF-κB reporter, IκBα degradation, and bortezomib survival assays

    PMID:29279332

    Open questions at the time
    • Surface receptor not yet identified at this stage
    • Mechanism of proteasome-independent IκBα degradation unresolved
  6. 2018 High

    Connected HAPLN1 to tissue mechanics and to age-related barrier function, showing it drives HA-dependent cortical folding and modulates endothelial permeability via VE-cadherin.

    Evidence Ex vivo human neocortex culture with CD168 blockade and ERK inhibition; reciprocal recombinant-protein and siRNA permeability assays plus in vivo reconstitution

    PMID:30078576 PMID:30279172

    Open questions at the time
    • Direct biochemical link between HAPLN1 and VE-cadherin not established
    • Cell-type specificity of mechanical effects incomplete
  7. 2020 Medium

    Defined HAPLN1 subcellular and pericellular distribution and a TGF-β-independent route to myofibroblast conversion.

    Evidence Confocal immunocytochemistry and exogenous HAPLN1 plus aggrecan G1 addition with α-SMA quantification in lung fibroblasts

    PMID:33064036

    Open questions at the time
    • Function of nuclear HAPLN1 staining unknown
    • Mechanism of myofibroblast induction not dissected
  8. 2021 Medium

    Placed HAPLN1 in the tumor stroma as a CAF-derived effector, showing TGF-β1/Smad2/3-driven HAPLN1 remodels collagen to promote invasion.

    Evidence Spheroid invasion, xenograft, and SHG collagen imaging in gastric cancer with TGF-β1/Smad2/3 pathway analysis

    PMID:34724589

    Open questions at the time
    • Direct molecular target of HAPLN1 in collagen remodeling unclear
    • Single tumor type
  9. 2022 Medium

    Identified the myeloma surface receptor and a second active domain, defining a CH60–TLR4 complex and the PTR1 module as drivers of HAPLN1 signaling and multi-drug resistance.

    Evidence Cell-surface biotinylation and Co-IP identifying CH60-TLR4; PTR1 domain protein treatment with survival and gene-expression assays in MM cells

    PMID:36480501 PMID:36625202

    Open questions at the time
    • Stoichiometry and direct binding affinity of HAPLN1-CH60-TLR4 not quantified
    • Single lab for both findings
  10. 2022 High

    Demonstrated an in vivo regenerative role, showing hapln1-expressing epicardial cells deposit HA to drive cardiomyocyte proliferation in zebrafish.

    Evidence scRNA-seq, induced cell depletion, and hapln1b genetic inactivation with HA deposition and cardiomyocyte proliferation readouts

    PMID:35652354

    Open questions at the time
    • Mammalian conservation of the regenerative role untested
    • Signaling axis downstream of HA deposition not defined here
  11. 2023 Medium

    Expanded the mechanistic repertoire across neural, vascular, metastatic, and protective contexts, defining distinct HA- and proteoglycan-coupled effector pathways.

    Evidence Crtl1-KO fear extinction and PNN analysis; TNFR2/TNF/HA peritoneal metastasis model; NF-κB–IFN-β–STAT1 matrikine BM-homing assays; CD44-dependent TGF-βRI/Smad3 and SIRT/senescence analysis; Nrf2/ARE-mediated NLRP3 inhibition in spinal cord injury

    PMID:37022587 PMID:37095087 PMID:37587649 PMID:37647592 PMID:38607990

    Open questions at the time
    • Whether one biochemical activity underlies these divergent outputs is unresolved
    • TGF-β receptor-subtype selectivity differs between tissues
    • Several pathways rest on single-lab evidence
  12. 2024 Medium

    Refined the vascular-integrity and regenerative mechanisms and characterized site-specific glycosylation, linking HAPLN1 to HA-ICAM1-VE-cadherin control, versican-GDF11 trapping, and glycan-dependent stability.

    Evidence Recombinant HAPLN1 ECM addition with ICAM1/VE-cadherin assays; versican-GDF11 binding and SMAD2/3 signaling in hiPSC-CMs; HaloTag-HAPLN1 live imaging of neuronal ECM; nano-LC-MS/MS site-specific N-glycopeptide analysis

    PMID:38246450 PMID:38472454 PMID:38618242 PMID:39251350

    Open questions at the time
    • Functional roles of Asn6/Asn41 glycans inferred from composition, not directly tested
    • Direct versican-GDF11-HAPLN1 ternary structure not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether the diverse signaling outputs attributed to HAPLN1 (NF-κB, STAT1, TGF-β/SMAD, ERK, Nrf2, TNFR2) arise from a single conserved biochemical activity (HA/proteoglycan organization) or from distinct, context-specific receptor engagements by released matrikine fragments.
  • No unifying receptor model across tissues
  • Relationship between full-length link function and matrikine signaling untested
  • Structural basis of domain-specific activities not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3
Partners
ASPNCD44GDF11HMMRHSPD1TLR4TNFRSF1BVCAN
Complex memberships
hyaluronan-proteoglycan complexperineuronal net

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 HAPLN1 (Crtl1) stabilizes the interaction between hyaluronan (HA) and versican in the extracellular matrix; Crtl1-deficient mice display cardiac malformations including AV septal and myocardial defects, accompanied by significant reduction in versican protein levels, establishing HAPLN1 as required for versican stability and cardiac development. Knockout mouse (Crtl1-/-), immunohistochemistry, expression analysis Developmental biology High 17822691
2018 HAPLN1, together with lumican and collagen I (HLC), causes hyaluronic acid (HA)-dependent folding of the developing human neocortex. HLC addition to human fetal neocortex cultures induced local tissue stiffness changes, cortical plate folding, and increased HA levels; these effects required the HA receptor CD168 and downstream ERK signaling, and loss of HA reduced HLC-induced folding. Ex vivo human fetal neocortex culture, ECM protein addition, HA receptor blocking, ERK inhibition, functional folding assay Neuron High 30078576
2018 Age-related decrease in HAPLN1 in the lymphatic ECM increases endothelial permeability via modulation of VE-cadherin junctions. Recombinant HAPLN1 added to aged fibroblast ECMs reduced endothelial permeability, while HAPLN1 knockdown in young fibroblasts increased permeability. In vivo reconstitution of HAPLN1 in aged mice increased lymph node metastases but reduced visceral metastases. Recombinant protein addition, siRNA knockdown, endothelial permeability assay, VE-cadherin junction imaging, in vivo mouse reconstitution experiment Cancer discovery High 30279172
2009 The SP-IgV domain of HAPLN1 is sufficient to increase tumorigenic properties (proliferation, motility, invasion, soft-agar colony formation) of mesothelioma cells, identifying the IgV domain as the functionally active domain for pro-tumorigenic activity. Transfection of full-length HAPLN1 and domain constructs into mesothelioma cells, proliferation/motility/invasion/soft-agar assays Clinical cancer research Medium 19351750
2010 LH/hCG-induced Hapln1 expression in rat granulosa cells is mediated by RUNX1 and RUNX2 transcription factors binding directly to the Hapln1 promoter; this induction requires PKA, PI3K, p38 MAPK, EGF signaling, and prostaglandin synthesis. HAPLN1 promotes granulosa cell survival and reduces apoptosis. siRNA knockdown of Runx1/2, dominant-negative RUNX, chromatin immunoprecipitation (ChIP), luciferase reporter with RUNX site mutation, pharmacological inhibitors, cell viability assay Molecular endocrinology High 20339004
2003 FSH and IGF-I synergistically induce Crtl1 (HAPLN1) production in rat granulosa cells via PI3K/Akt signaling; inhibition of PI3K (LY294002, wortmannin) abrogated FSH- and IGF-I-dependent Crtl1 production, while p38 MAPK inhibition caused partial (~30%) reduction. Primary granulosa cell culture, pharmacological inhibitors (PI3K, p38 MAPK), immunoblotting, RT-PCR Endocrinology Medium 12586755
2017 HAPLN1, produced by bone marrow stromal cells, activates a bortezomib-resistant atypical NF-κB pathway in multiple myeloma cells involving IκBα degradation that is resistant to proteasome inhibition, thereby promoting drug resistance. HAPLN1 protein treatment of MM cells, NF-κB reporter assays, IκBα degradation assay, bortezomib proteasome activity assay, cell survival assay The Journal of biological chemistry Medium 29279332
2021 Gastric cancer cells activate fibroblasts to upregulate HAPLN1 expression via TGF-β1/Smad2/3 signaling. CAF-derived HAPLN1 promotes tumor migration and invasion through ECM remodeling, as demonstrated by SHG imaging of collagen fiber changes. Spheroid cell invasion assay, xenograft model, second harmonic generation (SHG) imaging, TGF-β1/Smad2/3 pathway analysis Gastric cancer Medium 34724589
2022 In zebrafish, hapln1b-expressing epicardial cells deposit hyaluronic acid at cardiac injury sites to support cardiomyocyte proliferation and heart regeneration. Genetic depletion of hapln1-expressing cells or inactivation of hapln1b disrupted HA deposition and inhibited cardiomyocyte proliferation. hapln1-expressing epicardial cells also direct cardiomyocyte expansion during juvenile cardiac wall maturation. Single-cell RNA sequencing, induced genetic cell depletion, genetic inactivation of hapln1b, HA deposition assay, cardiomyocyte proliferation assay (zebrafish) Circulation High 35652354
2023 HAPLN1 promotes perineuronal net (PNN) formation and stabilizes chondroitin sulfate proteoglycan (CSPG) condensation; Crtl1-KO mice display normal CSPG levels but disrupted CSPG condensation into PNNs. This PNN disruption renders fear memories susceptible to erasure after extinction protocol and abolishes amygdala neural activation (Zif268) following extinction in conditioned mice. Crtl1 knockout mouse, fear extinction behavioral assay, Zif268 immunostaining in amygdala, pupil dynamics analysis Molecular neurobiology Medium 37022587
2022 The proteoglycan tandem repeat 1 (PTR1) domain of HAPLN1 induces cell survival gene expression and confers resistance to multiple drug classes (proteasome inhibitors, steroids, immunomodulatory drugs, DNA damaging agents) in multiple myeloma cells. PTR1 domain protein treatment of MM cell lines, cell survival assays, gene expression analysis PloS one Medium 36480501
2022 Cell surface chaperonin 60 (CH60) acts as a direct binding partner of HAPLN1 on multiple myeloma cells, and CH60 specifically interacts with TLR4 to evoke HAPLN1-induced NF-κB signaling, anti-apoptotic gene transcription, and drug resistance. Unbiased cell surface biotinylation assay, co-immunoprecipitation, NF-κB reporter assay, apoptosis assay, drug resistance assay Life science alliance Medium 36625202
2023 A HAPLN1-derived matrikine activates STAT1 in multiple myeloma cells via NF-κB-induced IFN-β signaling, promoting MM cell adhesion to fibronectin, endothelial cells, and stromal cells, and inducing chemotactic/chemokinetic migration and bone marrow homing in a mouse xenograft model. Matrikine peptide treatment of MM cells, xenograft BM homing assay, STAT1 activation assay, NF-κB assay, IFN-β measurement, adhesion and migration assays Blood advances Medium 37647592
2023 HAPLN1 promotes peritoneal metastasis of pancreatic cancer by upregulating tumor necrosis factor receptor 2 (TNFR2) on cancer cells, which facilitates TNF-mediated upregulation of hyaluronan (HA) production, thereby promoting EMT, stemness, invasion, and immunomodulation. Mouse peritoneal carcinomatosis model, TNFR2 receptor expression analysis, HA production assay, EMT/stemness markers, in vivo tumor spreading assay Nature communications Medium 37095087
2023 Recombinant HAPLN1 increases TGF-β receptor I (but not TGF-β RII) protein levels in human alveolar epithelial cells in a CD44-dependent manner, and enhances Smad3 (but not Smad2) phosphorylation upon TGF-β1 stimulation. HAPLN1 also increases SIRT1/2/6 levels and regulates cellular senescence markers (p53, p21, p16). Recombinant protein treatment of alveolar epithelial cells, western blotting of receptor and signaling components, CD44-dependent blocking experiment, mouse emphysema model Molecules and cells Medium 37587649
2020 HAPLN1 localizes to pericellular matrices in human lung fibroblasts, associating with both versican and hyaluronan. Exogenous HAPLN1 (together with aggrecan G1 domain) promotes myofibroblast conversion (α-SMA upregulation) and compaction of hyaluronan-rich ECM. Nuclear HAPLN1 staining increases after myofibroblast induction and redistributes to cytosol during mitosis. Immunocytochemistry, confocal microscopy, exogenous HAPLN1 protein addition, α-SMA quantification, TGF-β1-free myofibroblast induction assay The journal of histochemistry and cytochemistry Medium 33064036
2023 Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by binding to versican, which traps GDF11; this complex is required for rhHapln1-mediated activation of TGF-β/SMAD2/3 signaling that stimulates cardiomyocyte dedifferentiation and proliferation. Recombinant Hapln1 treatment of hiPSC-CMs, versican-GDF11 interaction assay, GDF11 requirement test, TGF-β/SMAD2/3 signaling western blot, adult mouse myocardial infarction model Journal of pharmaceutical analysis Medium 38618242
2024 HAPLN1 in the dermal ECM maintains melanoma-associated blood vessel integrity by increasing hyaluronic acid and decreasing endothelial ICAM1 expression in an indirect, matrix-dependent manner. ICAM1 phosphorylates and internalizes VE-cadherin, causing vascular permeability; HAPLN1 loss with aging leads to increased ICAM1 and compromised vascular integrity. Recombinant HAPLN1 addition to ECM, ICAM1 expression analysis, VE-cadherin phosphorylation/internalization assay, ICAM1 blocking in vivo mouse experiment Nature aging Medium 38472454
2023 HAPLN1 inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway in spinal cord injury models; HAPLN1 administration increased Nrf2/HO-1/NQO-1, decreased NLRP3/ASC/caspase-1/IL-1β, and improved motor neuron survival. Inhibition of Nrf2 with ML385 abolished these protective effects. In vitro (H2O2-treated PC12 cells) and in vivo SCI mouse model, HAPLN1 administration, Nrf2 inhibition (ML385), western blot, ELISA, Nissl staining, TUNEL assay Biotechnology and applied biochemistry Medium 38607990
2024 N-glycosylation of HAPLN1 at two sites (Asn 6 and Asn 41) differs in composition and function: Asn 6 bears predominantly tri- and tetra-sialylated glycans (protecting HAPLN1 from proteolysis, extending half-life), while Asn 41 (located in the Ig-like domain that interacts with proteoglycan) bears predominantly di-fucosylated glycans and sialyl-Lewis X/a epitopes (supporting molecular interactions). Nano-LC-MS/MS of trypsin-treated recombinant human HAPLN1 from CHO cells, site-specific N-glycopeptide identification International journal of biological macromolecules Medium 38246450
2024 HaloTag-HAPLN1 fusion probe reveals spatial and temporal regulation of hyaluronan-scaffolded ECM deposition in neurons; excitatory neurons possess previously unidentified ECM architecture, and ECM assembly around dendrites is developmentally regulated. Dual-color birthdating demonstrates ECM assembly dynamics in vitro and in vivo. HaloTag-HAPLN1 fusion protein expression in primary rat neuronal cultures and mouse brain, live imaging, dual-color birthdating, confocal microscopy The Journal of neuroscience Medium 39251350
2023 HAPLN1 interacts with ASPN (asporin) in bone marrow mesenchymal stromal cells; combined knockdown of ASPN and HAPLN1 synergistically increases osteogenic marker expression (ALP, OPN, OCN, COL1A1) and ECM mineralization in BMSCs, while decreasing osteoclast markers (Nfatc1, c-Fos). Co-immunoprecipitation (ASPN-HAPLN1 interaction), siRNA knockdown (single and dual), osteogenic differentiation assays, ECM mineralization assay in OVX mouse-derived BMSCs Orthopaedic surgery Low 37427673
2022 HAPLN1 secreted by RA fibroblast-like synoviocytes promotes macrophage polarization towards the M1 (pro-inflammatory) phenotype, increasing M1/Mϕ ratio and expression of IL-1β, TNF-α, and iNOS. Recombinant HAPLN1 (rHAPLN1) treatment of THP-1-derived macrophages, HAPLN1OE/si-HAPLN1 transfection of RA-FLS co-cultured with macrophages, flow cytometry, qPCR, western blot Xi bao yu fen zi mian yi xue za zhi Low 40415620
2023 Recombinant HAPLN1 selectively increases TGF-β receptor II (not TGF-β RI) levels in human hair matrix cells and activates the ERK1/2 signaling pathway, promoting hair matrix cell proliferation and accelerating entry of hair follicles into the anagen phase. Recombinant HAPLN1 treatment of human hair matrix cells, western blotting of TGF-β receptors, ERK1/2 phosphorylation assay, mouse hair cycle experiment Biomolecules & therapeutics Low 37551604
2026 In zebrafish spinal cord injury, hapln1 is upregulated in progenitor cells and is required for hyaluronic acid-CD44b-mediated progenitor cell proliferation and spontaneous spinal cord regeneration; loss of hapln1a/b or ablation of hapln1+ cells reduced progenitor activation and hindered recovery. Single-cell RNA sequencing, loss-of-function genetics (hapln1a/b), cell ablation, in vivo and in vitro CD44b signaling assays (zebrafish) bioRxivpreprint Medium 41959443

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Extracellular Matrix Components HAPLN1, Lumican, and Collagen I Cause Hyaluronic Acid-Dependent Folding of the Developing Human Neocortex. Neuron 140 30078576
2018 Age-Related Changes in HAPLN1 Increase Lymphatic Permeability and Affect Routes of Melanoma Metastasis. Cancer discovery 131 30279172
2021 Cancer-associated fibroblasts-derived HAPLN1 promotes tumour invasion through extracellular matrix remodeling in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 95 34724589
2007 Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development. Developmental biology 71 17822691
2022 hapln1 Defines an Epicardial Cell Subpopulation Required for Cardiomyocyte Expansion During Heart Morphogenesis and Regeneration. Circulation 52 35652354
2010 Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 48 20953637
2010 Periovulatory expression of hyaluronan and proteoglycan link protein 1 (Hapln1) in the rat ovary: hormonal regulation and potential function. Molecular endocrinology (Baltimore, Md.) 41 20339004
2009 Protumorigenic role of HAPLN1 and its IgV domain in malignant pleural mesothelioma. Clinical cancer research : an official journal of the American Association for Cancer Research 39 19351750
1997 Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study. Arthritis and rheumatism 39 9336408
2017 Hyaluronan and proteoglycan link protein 1 (HAPLN1) activates bortezomib-resistant NF-κB activity and increases drug resistance in multiple myeloma. The Journal of biological chemistry 38 29279332
2023 HAPLN1 potentiates peritoneal metastasis in pancreatic cancer. Nature communications 37 37095087
1999 Refined genetic and physical localization of the Wagner disease (WGN1) locus and the genes CRTL1 and CSPG2 to a 2- to 2.5-cM region of chromosome 5q14.3. Genomics 33 10198161
2020 Metformin, an AMPK Activator, Inhibits Activation of FLSs but Promotes HAPLN1 Secretion. Molecular therapy. Methods & clinical development 31 32518807
1990 Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene. Genomics 31 2286376
2016 De novo HAPLN1 expression hallmarks Wnt-induced stem cell and fibrogenic networks leading to aggressive human hepatocellular carcinomas. Oncotarget 29 27191501
2003 Follicle-stimulating hormone and insulin-like growth factor I synergistically induce up-regulation of cartilage link protein (Crtl1) via activation of phosphatidylinositol-dependent kinase/Akt in rat granulosa cells. Endocrinology 27 12586755
2013 Abnormal expression of chondroitin sulphate N-acetylgalactosaminyltransferase 1 and Hapln-1 in cartilage with Kashin-Beck disease and primary osteoarthritis. International orthopaedics 25 23748413
2020 A Role for HAPLN1 During Phenotypic Modulation of Human Lung Fibroblasts In Vitro. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 24 33064036
2022 HAPLN1 Affects Cell Viability and Promotes the Pro-Inflammatory Phenotype of Fibroblast-Like Synoviocytes. Frontiers in immunology 22 35720292
2024 Age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 in melanoma. Nature aging 20 38472454
2023 Selective Disruption of Perineuronal Nets in Mice Lacking Crtl1 is Sufficient to Make Fear Memories Susceptible to Erasure. Molecular neurobiology 18 37022587
2008 Molecular cloning and developmental expression of a hyaluronan and proteoglycan link protein gene, crtl1/hapln1, in zebrafish. Zoological science 13 19267601
1992 Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia. American journal of medical genetics 11 1442879
2023 ASPN Synergizes with HAPLN1 to Inhibit the Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells and Extracellular Matrix Mineralization of Osteoblasts. Orthopaedic surgery 8 37427673
2023 Recombinant Human HAPLN1 Mitigates Pulmonary Emphysema by Increasing TGF-β Receptor I and Sirtuins Levels in Human Alveolar Epithelial Cells. Molecules and cells 8 37587649
2022 The Effects of TNF-α Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-β1 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis. Journal of clinical medicine 7 35407621
1999 Characterization and chromosome location of the mouse link protein gene (Crtl1). Cytogenetics and cell genetics 6 10640815
1991 GT repeat polymorphism in the human proteoglycan link gene (CRTL1) promoter region. Nucleic acids research 6 1754418
2024 The effects of hyaluronan and proteoglycan link protein 1 (HAPLN1) in ameliorating spinal cord injury mediated by Nrf2. Biotechnology and applied biochemistry 5 38607990
2023 A Novel Role of Hyaluronic Acid and Proteoglycan Link Protein 1 (HAPLN1) in Delaying Vascular Endothelial Cell Senescence. Biomolecules & therapeutics 5 37551651
2024 Dynamic Organization of Neuronal Extracellular Matrix Revealed by HaloTag-HAPLN1. The Journal of neuroscience : the official journal of the Society for Neuroscience 4 39251350
2023 HAPLN1 matrikine: a bone marrow homing factor linked to poor outcomes in patients with MM. Blood advances 4 37647592
2023 Perineuronal nets and the neuronal extracellular matrix can be imaged by genetically encoded labeling of HAPLN1 in vitro and in vivo. bioRxiv : the preprint server for biology 4 38076839
2022 HAPLN1 confers multiple myeloma cell resistance to several classes of therapeutic drugs. PloS one 4 36480501
2020 Significant association of serum autoantibodies to TYMS, HAPLN1 and IGFBP5 with early stage canine malignant mammary tumours. Veterinary and comparative oncology 4 33038064
2025 Identification and functional characterization of hub genes CLTA, EDIL3, HAPLN1, and HIP1 as diagnostic biomarkers and therapeutic targets in thyroid cancer and Hashimoto's thyroiditis. Clinical and experimental medicine 3 40372556
2023 Novel Effect of Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1) on Hair Follicle Cells Proliferation and Hair Growth. Biomolecules & therapeutics 3 37551604
2022 Ectopic CH60 mediates HAPLN1-induced cell survival signaling in multiple myeloma. Life science alliance 3 36625202
2024 HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway. BMC cardiovascular disorders 2 38580957
2024 Novel extracellular matrix architecture on excitatory neurons revealed by HaloTag-HAPLN1. bioRxiv : the preprint server for biology 2 38585814
2023 Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping. Journal of pharmaceutical analysis 2 38618242
1991 TaqI and HaeIII RFLP polymorphisms in human proteoglycan link gene (CRTL1). Nucleic acids research 2 1684430
2024 Comparison of sialylated and fucosylated N-glycans attached to Asn 6 and Asn 41 with different roles in hyaluronan and proteoglycan link protein 1 (HAPLN1). International journal of biological macromolecules 1 38246450
2026 Hapln1-HA signaling promotes progenitor cell proliferation and spinal cord regeneration. bioRxiv : the preprint server for biology 0 41959443
2025 [HAPLN1 secreted by synovial fibroblasts in rheumatoid arthritis promotes macrophage polarization towards the M1 phenotype]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 40415620
2025 HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes. Inflammation 0 40682641
2024 Upregulation of serum miR-4429 discriminates chronic heart failure patients and regulates cardiomyocyte injury via modulating HAPLN1. Minerva cardiology and angiology 0 39283199
2024 Analysis of ANO6, HAPLN1, and EDIL3 Polymorphisms in Patients with Ankylosing Spondylitis in a Chinese Han Population: A Case-Control Study. Genetic testing and molecular biomarkers 0 39358671

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