Hyaluronan and proteoglycan link protein 1 · UniProt P10915
HAPLN1 is a secreted extracellular matrix glycoprotein that cross-links hyaluronan (HA) and proteoglycans—principally versican and aggrecan—to stabilize pericellular and interstitial matrices, thereby governing tissue architecture in contexts ranging from cardiac development and cortical folding to perineuronal net condensation and vascular integrity (PMID:17822691, PMID:30078576, PMID:30279172, PMID:37022587). Beyond its structural role, HAPLN1 functions as a signaling scaffold: it engages CD44 to activate ERK and TGF-β/Smad pathways controlling cell proliferation and differentiation (PMID:30078576, PMID:37587649, PMID:38618242), and on myeloma cells it binds cell-surface chaperonin 60 (HSPD1), which couples to TLR4 to drive an atypical, proteasome-independent NF-κB pathway that confers multi-drug resistance (PMID:36625202, PMID:29279332). HAPLN1 additionally regulates vascular permeability by maintaining VE-cadherin junctions through HA-dependent suppression of ICAM1, and its age-related loss increases endothelial leakiness and redirects metastatic dissemination (PMID:30279172, PMID:38472454).
Determination of the full-length sequence and chromosomal locus of human HAPLN1 provided the molecular identity needed for all subsequent functional studies.
Evidence cDNA cloning, sequencing, and chromosomal mapping to 5q13-q14.1
Establishing that FSH/IGF-I induce HAPLN1 via PI3K-Akt in granulosa cells revealed the first signal-transduction pathway controlling its expression and linked HAPLN1 to ovarian physiology.
Evidence Primary rat granulosa cell culture with pharmacological PI3K and p38 inhibitors, immunoblotting
Crtl1-knockout mice demonstrated that HAPLN1 is essential for stabilizing the versican-HA matrix in vivo and that its loss causes structural cardiac malformations, establishing a causal developmental role.
Evidence Crtl1 knockout mouse with histology, immunohistochemistry for versican, epistasis with versican haploinsufficiency
Domain dissection showing the SP-IgV region drives tumorigenic cell behaviors identified the first functional domain responsible for HAPLN1's pro-proliferative and pro-invasive activities.
Evidence Transfection of full-length and domain constructs in mesothelioma cells with proliferation, motility, invasion, and colony formation assays
ChIP and promoter mutagenesis demonstrated that RUNX1/RUNX2 directly bind the HAPLN1 promoter downstream of LH/PKA signaling, placing HAPLN1 transcription under gonadotropin control and linking it to granulosa cell survival.
Evidence Chromatin immunoprecipitation, luciferase reporters with RUNX site mutations, siRNA and dominant-negative RUNX in granulosa cells
Demonstrating that HAPLN1 activates an atypical, proteasome-independent NF-κB pathway in myeloma cells explained how stromal HAPLN1 confers bortezomib resistance, revealing a paracrine drug-resistance mechanism.
Evidence Recombinant HAPLN1 treatment, NF-κB reporters, IκBα degradation kinetics, proteasome activity assays, drug-resistance viability assays in MM cells
Two landmark studies established HAPLN1 as a signaling-competent ECM organizer: one showed HAPLN1 drives cortical folding through HA/CD44/ERK signaling, and the other showed age-related HAPLN1 loss disrupts VE-cadherin junctions to increase vascular permeability and redirect melanoma metastasis.
Evidence Ex vivo human fetal cortex with pharmacological CD44/ERK inhibition (cortical folding); in vitro permeability with recombinant HAPLN1 and siRNA, in vivo HAPLN1 reconstitution in aged mice (vascular integrity)
Showing that cancer cells induce HAPLN1 in fibroblasts via TGF-β1/Smad2/3, which then remodels collagen to promote invasion, defined a bidirectional tumor-stroma signaling loop centered on HAPLN1.
Evidence Gastric cancer spheroid invasion, SHG collagen imaging, nude mouse xenograft, TGF-β1 pathway inhibition
Identification of cell-surface chaperonin 60 (HSPD1/CH60) as the direct HAPLN1 receptor on myeloma cells, coupling through TLR4 to NF-κB, resolved the long-standing question of how an ECM protein activates intracellular signaling in this context.
Evidence Unbiased surface biotinylation, co-immunoprecipitation of CH60-TLR4, NF-κB reporter and drug resistance assays
Genetic studies in zebrafish showed hapln1-expressing epicardial cells are required for HA deposition around cardiomyocytes and for their proliferation during heart regeneration, extending HAPLN1's cardiac role from developmental morphogenesis to adult regenerative biology.
Evidence scRNA-seq, genetic cell depletion and hapln1b loss-of-function in zebrafish, HA and cardiomyocyte proliferation quantification
The PTR1 domain was shown sufficient to confer multi-drug resistance in myeloma, narrowing the functional determinant beyond the earlier SP-IgV finding and complementing the CH60/TLR4 receptor axis.
Evidence PTR1 recombinant protein treatment of MM cell lines with multi-class drug resistance and gene expression assays
Crtl1-KO mice with disrupted PNN condensation but normal CSPG levels showed erasable fear memories, establishing that HAPLN1-dependent PNN structural integrity—not merely proteoglycan abundance—is required for memory persistence.
Evidence Fear conditioning/extinction in Crtl1-KO mice, freezing behavior, Zif268 immunostaining of amygdala
A HAPLN1 matrikine fragment was shown to drive myeloma cell adhesion and BM homing through NF-κB→IFN-β→STAT1 signaling, revealing that proteolytic fragments of HAPLN1 possess distinct bioactivities beyond the full-length protein.
Evidence Adhesion/migration assays, mouse xenograft BM homing, NF-κB and STAT1 inhibition, IFN-β measurement
Demonstration that HAPLN1 traps GDF11 on versican to activate TGF-β/SMAD2/3-driven cardiomyocyte dedifferentiation and proliferation, with in vivo cardiac regeneration in mice, provided a growth-factor sequestration mechanism explaining HAPLN1's signaling potency beyond direct receptor engagement.
Evidence Pulldown of Hapln1-versican-GDF11 complex, SMAD2/3 phosphorylation, GDF11 knockdown rescue, adult mouse MI model
N-glycan profiling revealed site-specific glycosylation (tri/tetra-sialylation at Asn6 protecting against proteolysis; sialyl-Lewis X/a at Asn41 enhancing proteoglycan binding), providing the first post-translational structural insight into HAPLN1 stability and binding regulation.
Evidence Nano-LC-MS/MS of recombinant HAPLN1 with site-specific glycan analysis
Mechanistic dissection of the age-dependent vascular phenotype showed HAPLN1 maintains endothelial barrier integrity through HA-mediated suppression of ICAM1, which when elevated phosphorylates and internalizes VE-cadherin, completing the molecular pathway from ECM loss to vascular leakiness.
Evidence ECM reconstitution with recombinant HAPLN1, HAPLN1 knockdown, ICAM1-VE-cadherin pathway dissection, in vivo ICAM1 blockade in aged melanoma-bearing mice
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2018 | HAPLN1, together with lumican and collagen I (HLC), causes cortical plate folding in human fetal neocortex by increasing hyaluronic acid (HA) levels, requiring the HA-receptor CD44 (CD168/RHAMM) and downstream ERK signaling; loss of HA reduced HLC-induced and physiological nascent folds. | Ex vivo culture of human fetal neocortex with ECM component addition, HA quantification, pharmacological inhibition of CD168 and ERK, tissue stiffness measurement | Neuron | High | 30078576 |
| 2018 | Age-related loss of HAPLN1 in dermal/lymphatic ECM increases lymphatic endothelial permeability by disrupting VE-cadherin junctions; recombinant HAPLN1 added to aged fibroblast ECMs reduced endothelial permeability, while HAPLN1 knockdown in young fibroblasts increased it. In vivo reconstitution of HAPLN1 in aged mice redirected melanoma metastasis toward lymph nodes and away from visceral sites. | In vitro permeability assay with recombinant HAPLN1, siRNA knockdown of HAPLN1, VE-cadherin junction imaging, in vivo HAPLN1 reconstitution in aged mice with tumor metastasis readout | Cancer discovery | High | 30279172 |
| 2007 | Crtl1 (mouse HAPLN1 ortholog) stabilizes the interaction between hyaluronan and versican in cardiac ECM; Crtl1-deficient mice show cardiac malformations (AV septal and myocardial defects) accompanied by significantly reduced versican levels, placing Crtl1 upstream of versican stability in heart development. | Crtl1 knockout mouse, immunohistochemistry, histological analysis, versican expression studies | Developmental biology | High | 17822691 |
| 2017 | HAPLN1 produced by bone marrow stromal cells activates an atypical, bortezomib-resistant NF-κB pathway in multiple myeloma cells involving IκBα degradation that is independent of proteasome activity, thereby conferring drug resistance. | Recombinant HAPLN1 treatment of MM cells, NF-κB reporter assays, IκBα immunoblotting, proteasome activity assays, bortezomib resistance cell viability assays | The Journal of biological chemistry | High | 29279332 |
| 2021 | Cancer-associated fibroblast-derived HAPLN1 promotes gastric cancer invasion through ECM remodeling (collagen fiber reorganization detected by second harmonic generation imaging); gastric cancer cells upregulate HAPLN1 in fibroblasts via TGF-β1/Smad2/3 signaling. | Spheroid invasion assay, nude mouse xenograft, second harmonic generation (SHG) imaging of collagen, siRNA knockdown, TGF-β1 pathway inhibition | Gastric cancer | High | 34724589 |
| 2009 | HAPLN1 overexpression increases tumorigenic properties (proliferation, motility, invasion, soft-agar colony formation) of mesothelioma cells; the SP-IgV domain of HAPLN1 is specifically responsible for these protumorigenic activities. | Transfection of full-length HAPLN1 and domain constructs, proliferation/motility/invasion/colony formation assays, DNA copy number analysis | Clinical cancer research | Medium | 19351750 |
| 2010 | In periovulatory granulosa cells, LH/hCG-induced HAPLN1 expression is mediated by PKA, PI3K, p38 MAPK, EGF signaling, and prostaglandin synthesis pathways; RUNX1 and RUNX2 transcription factors bind the HAPLN1 promoter (confirmed by ChIP) and are required for LH-induced expression. HAPLN1 promotes granulosa cell survival and reduces apoptosis. | Chromatin immunoprecipitation (ChIP), luciferase reporter assays with RUNX binding site mutations, siRNA knockdown of Runx1/2, dominant-negative RUNX, pharmacological inhibition of signaling pathways, cell viability and apoptosis assays | Molecular endocrinology | High | 20339004 |
| 2003 | FSH and IGF-I synergistically induce Crtl1/HAPLN1 production in rat granulosa cells via PI3K-Akt signaling; PI3K inhibitors (LY294002, wortmannin) abrogate both FSH- and IGF-I-induced Crtl1 production, while p38 MAPK inhibition gives partial (~30%) reduction. | Primary granulosa cell culture, immunoblotting, pharmacological inhibition of PI3K and p38, mRNA expression analysis | Endocrinology | Medium | 12586755 |
| 2023 | HAPLN1 promotes peritoneal metastasis of pancreatic cancer by upregulating TNFR2, which facilitates TNF-mediated hyaluronan production, thereby enhancing EMT, stemness, invasion, and immunomodulation in a permissive microenvironment. | Mouse peritoneal carcinomatosis model, HAPLN1 overexpression/knockdown, TNFR2 expression analysis, HA quantification, immunomodulation assays | Nature communications | High | 37095087 |
| 2022 | In zebrafish, hapln1-expressing epicardial cells are required for hyaluronic acid deposition around dedifferentiated cardiomyocytes; genetic depletion of hapln1-expressing cells or inactivation of hapln1b disrupts HA matrix, impairs cardiomyocyte proliferation, and inhibits heart regeneration. | Single-cell RNA sequencing, genetic cell depletion, hapln1b loss-of-function genetics, HA deposition assay, cardiomyocyte proliferation quantification in zebrafish | Circulation | High | 35652354 |
| 2022 | HAPLN1 promotes proliferation but inhibits migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), and upregulates pro-inflammatory factors (TNF-α, MMPs, IL-6); HAPLN1 expression positively correlates with AMPK levels and modulates AMPK-α signaling. | siRNA knockdown, overexpression vector, recombinant HAPLN1 treatment, qPCR, proteomics, mRNA-seq of RA-FLSs | Frontiers in immunology | Medium | 35720292 |
| 2022 | The PTR1 domain of HAPLN1 induces survival gene expression and confers resistance to multiple drug classes (proteasome inhibitors, steroids, immunomodulatory drugs, DNA-damaging agents) in multiple myeloma cells. | PTR1 domain recombinant protein treatment of MM cell lines, drug resistance assays, gene expression analysis | PloS one | Medium | 36480501 |
| 2022 | Cell surface chaperonin 60 (CH60/HSPD1) is the direct binding partner of HAPLN1 on multiple myeloma cells; ectopic CH60 interacts with TLR4 to activate HAPLN1-induced NF-κB signaling, anti-apoptotic gene transcription, and drug resistance. | Unbiased cell surface biotinylation assay, co-immunoprecipitation of CH60 with TLR4, NF-κB reporter assays, apoptosis and drug resistance assays | Life science alliance | High | 36625202 |
| 2023 | A HAPLN1 matrikine (proteolytic fragment) induces multiple myeloma cell adhesion to fibronectin, endothelial and stromal cells, and drives chemotactic/chemokinetic migration; this is mediated by NF-κB-induced IFN-β, which activates STAT1; in a mouse xenograft model, MM cells preferentially home to HAPLN1 matrikine-conditioned bone marrow. | Adhesion assays, migration/chemotaxis assays, mouse xenograft BM homing model, NF-κB and STAT1 inhibition, IFN-β measurement, signaling pathway analysis | Blood advances | High | 37647592 |
| 2023 | Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by binding versican, which traps GDF11; trapped GDF11 activates TGF-β/SMAD2/3 signaling, stimulating cardiomyocyte dedifferentiation and proliferation. Recombinant Hapln1 induces cardiac regeneration in adult mice with myocardial infarction. | hiPSC-CM culture with recombinant Hapln1, pulldown/binding assay of Hapln1-versican-GDF11, GDF11 knockdown rescue, SMAD2/3 phosphorylation, adult mouse MI model | Journal of pharmaceutical analysis | Medium | 38618242 |
| 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, enhancing phospho-Smad3 (but not Smad2) signaling upon TGF-β1 stimulation; rhHAPLN1 also increases SIRT1/2/6 levels and reduces acetylated p300, regulating cellular senescence markers. | Recombinant HAPLN1 treatment of alveolar epithelial cells, CD44 blockade, TGF-β receptor Western blotting, p-Smad2/3 assay, sirtuin quantification, mouse emphysema/COPD models | Molecules and cells | Medium | 37587649 |
| 2024 | HAPLN1 in dermal ECM maintains vascular integrity by increasing hyaluronic acid and decreasing endothelial ICAM1 expression; elevated ICAM1 phosphorylates and internalizes VE-cadherin, increasing vascular permeability. Blocking ICAM1 reduces tumor size and metastasis in older mice. | In vitro ECM reconstitution with recombinant HAPLN1, HAPLN1 knockdown in young fibroblasts, collagen/VE-cadherin/HA quantification, ICAM1 blockade in vivo in aged mice with melanoma | Nature aging | High | 38472454 |
| 2023 | Genetic disruption of perineuronal nets (PNNs) in Crtl1-KO mice (which have normal CSPG levels but impaired CSPG condensation into PNNs) makes fear memories susceptible to erasure by extinction training; conditioned Crtl1-KO mice show no amygdala neural activation (Zif268) after extinction, indicating PNN condensation is required for persistent fear memory. | Crtl1-KO mice, fear conditioning and extinction protocol, freezing behavior, pupil dynamics, Zif268 immunostaining of amygdala | Molecular neurobiology | High | 37022587 |
| 2020 | HAPLN1 localizes to pericellular matrices in human lung fibroblasts, associating with versican and hyaluronan; exogenous HAPLN1 (plus aggrecan G1) promotes myofibroblast formation (α-SMA upregulation) and compaction of hyaluronan-rich ECM even without TGF-β1, while full-length versican alone has no such effect. | Immunocytochemistry, confocal microscopy, exogenous HAPLN1/aggrecan G1/versican addition assays, α-SMA quantification, ECM compaction assay | The journal of histochemistry and cytochemistry | Medium | 33064036 |
| 2023 | HAPLN1 N-glycosylation at Asn6 (N-terminal region) is enriched in tri- and tetra-sialylated glycans that protect HAPLN1 from proteolysis, while Asn41 (Ig-like domain interacting with proteoglycan) carries more di-fucosylated glycans and sialyl-Lewis X/a epitopes that enhance binding affinity and stability. | Nano-LC-MS/MS of trypsin-treated recombinant rhHAPLN1, site-specific N-glycan structural analysis | International journal of biological macromolecules | Medium | 38246450 |
| 2025 | HAPLN1 secreted by RA fibroblast-like synoviocytes promotes M1 macrophage polarization; recombinant HAPLN1 increases M1/macrophage ratio and inflammatory factor levels (IL-1β, TNF-α, iNOS), while siHAPLN1 reduces these effects in a co-culture model. | THP-1-derived macrophage co-culture with HAPLN1OE or si-HAPLN1 RA-FLS, flow cytometry for M1/M2 ratio, qPCR and Western blot for inflammatory markers, CCK-8 assay | Xi bao yu fen zi mian yi xue za zhi | Medium | 40415620 |
| 2025 | HAPLN1 in arthritic chondrocytes activates PI3K/AKT/mTOR pathway phosphorylation and has dual effects: promoting ECM restoration (collagen II, TGF-β upregulation) while enhancing inflammatory mediator production (TNF-α, IL-6, MMPs, ADAMTS-5); ASPN interacts with HAPLN1 protein to synergistically suppress osteogenic differentiation and ECM mineralization. | Recombinant HAPLN1 treatment of IL-1β-treated chondrocytes, RNA sequencing, PI3K/AKT/mTOR Western blot, ASPN-HAPLN1 binding assay, transwell co-culture, BMSCs from OVX mice | Inflammation / Orthopaedic surgery | Medium | 37427673 40682641 |
| 2023 | Genetically encoded HaloTag-HAPLN1 fusion protein reveals spatial and temporal regulation of ECM deposition in neuronal cultures and mouse brain in vivo; HAPLN1-scaffolded ECM forms PNN-like structures around many CNS neurons beyond PV-positive interneurons, including excitatory neurons with developmentally regulated dendritic ECM. | HaloTag-HAPLN1 expression in primary rat neuronal cultures and mouse brain in vivo, dual-color birthdating, confocal imaging, sparse in vivo expression | The Journal of neuroscience | Medium | 39251350 |
| 2024 | HAPLN1 promotes hyaluronic acid deposition in digit tip wounds in vivo and reduces scar formation; overexpression of HAPLN1 in non-regenerating digit amputations induces bone repair, establishing a causal role for HAPLN1-HA axis in regenerative ECM mechanics. | In vivo HAPLN1 overexpression in mouse digit tip amputation model, HA quantification, scar and bone repair histology, hydrogel stiffness modeling | bioRxivpreprint | Medium | bio_10.1101_2024.12.04.626830 |
| 2026 | In zebrafish spinal cord injury, Hapln1 is upregulated in progenitor cells and is required for hyaluronan-CD44b-mediated progenitor cell proliferation; hapln1a/b loss-of-function reduces progenitor activation and impairs spontaneous functional recovery. | Cross-species single-cell transcriptomics, hapln1a/b loss-of-function genetics, hapln1+ cell ablation, in vivo and in vitro HA-CD44b signaling assays | bioRxivpreprint | Medium | 41959443 |
| 1990 | The complete amino acid sequence of human CRTL1 (HAPLN1) was determined from cDNA cloning; the protein is 354 residues and the gene was mapped to chromosome 5q13-q14.1. | cDNA library screening, cDNA sequencing, chromosomal mapping | Genomics | High | 2286376 |
| 2024 | miR-4429 negatively regulates HAPLN1 in cardiomyocytes; H2O2-induced injury increases miR-4429 and reduces HAPLN1; silencing miR-4429 alleviates cardiomyocyte injury, and knockdown of HAPLN1 reverses this protective effect, placing HAPLN1 downstream of miR-4429 in the cardioprotective pathway. | H2O2 cardiomyocyte injury model, miR-4429 and HAPLN1 expression analysis, cell transfection, CCK-8 viability, ROS measurement, rescue experiments | Minerva cardiology and angiology | Medium | 39283199 |
| 2023 | Mecp2-null astrocyte-conditioned media induces HAPLN1 expression and causes enhanced PNN formation on wildtype neurons, demonstrating a non-cell-autonomous role for Mecp2-null astrocytes in driving precocious PNN formation via HAPLN1 upregulation. | Conditioned media transfer from Mecp2-null to wildtype neurons, HAPLN1 expression assay, PNN immunostaining in Mecp2-null cortex | bioRxivpreprint | Medium | bio_10.1101_2025.08.13.670146 |
| 2023 | Recombinant HAPLN1 promotes hair matrix cell proliferation by selectively increasing TGF-β receptor II levels and activating ERK1/2 signaling via TGF-β2; HAPLN1 is preferentially expressed in the anagen phase of the hair cycle and accelerates entry into anagen in vivo. | Recombinant HAPLN1 treatment of human hair matrix cells, TGF-β receptor Western blot, ERK1/2 phosphorylation assay, hair cycle staging in mice | Biomolecules & therapeutics | Medium | 37551604 |
| 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 | 138 | 30078576 |
| 2018 | Age-Related Changes in HAPLN1 Increase Lymphatic Permeability and Affect Routes of Melanoma Metastasis. | Cancer discovery | 129 | 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 | 92 | 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 | 48 | 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 | 36 | 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 |
| 1990 | Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene. | Genomics | 31 | 2286376 |
| 2020 | Metformin, an AMPK Activator, Inhibits Activation of FLSs but Promotes HAPLN1 Secretion. | Molecular therapy. Methods & clinical development | 30 | 32518807 |
| 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 | 19 | 38472454 |
| 2023 | Selective Disruption of Perineuronal Nets in Mice Lacking Crtl1 is Sufficient to Make Fear Memories Susceptible to Erasure. | Molecular neurobiology | 17 | 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 | 4 | 38607990 |
| 2023 | A Novel Role of Hyaluronic Acid and Proteoglycan Link Protein 1 (HAPLN1) in Delaying Vascular Endothelial Cell Senescence. | Biomolecules & therapeutics | 4 | 37551651 |
| 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 |
| 2024 | Dynamic Organization of Neuronal Extracellular Matrix Revealed by HaloTag-HAPLN1. | The Journal of neuroscience : the official journal of the Society for Neuroscience | 3 | 39251350 |
| 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 |