Affinage

HSPG2

Basement membrane-specific heparan sulfate proteoglycan core protein · UniProt P98160

Length
4391 aa
Mass
468.8 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Perlecan (HSPG2) is a large, modular basement membrane heparan sulfate proteoglycan that functions as a multivalent signaling scaffold and structural organizer of extracellular matrices. Its N-terminal heparan sulfate chains (domain I) sequester and present FGF-2 to FGF receptors, forming obligate HS–FGF–FGFR ternary complexes essential for mitogenic signaling in contexts including neurogenesis, vascular smooth muscle proliferation, and pulmonary hypertension (PMID:7528102, PMID:9121441, PMID:24434631, PMID:25952902), while the protein core independently binds FGF-7, FGF-18, Hedgehog, semaphorin 3A, progranulin, LDL, and dystroglycan through domain-specific sites to regulate chondrocyte differentiation, axon guidance, lipoprotein retention, and neuromuscular junction assembly (PMID:10702276, PMID:17971291, PMID:12645928, PMID:29740048, PMID:25528754, PMID:16219760). Domain V (endorepellin) promotes AChR clustering via MuSK in a laminin-polymerization-dependent manner and rescues myopathy and angiogenesis defects in zebrafish, while chondroitin sulfate chains on cartilage perlecan accelerate collagen II fibril assembly, and proteolytic processing by MMP-7 at domain IV acts as a molecular switch converting Sema3A-mediated FAK inactivation and cell clustering to FAK activation and invasive cell dispersion (PMID:18426981, PMID:16956876, PMID:24833109). Perlecan-null mice exhibit perinatal-lethal chondrodysplasia with basement membrane failure under mechanical stress, and perlecan deficiency abolishes endothelium-dependent vascular relaxation by reducing eNOS expression and impairs osteocyte mechanosensory calcium signaling (PMID:10579729, PMID:10545953, PMID:25626871, PMID:31715337).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Establishing that perlecan is not merely a structural proteoglycan but a functional co-receptor that enables high-affinity FGF-2 binding to its receptor and drives angiogenesis in vivo answered the fundamental question of why basement membrane HSPGs are required for growth factor signaling.

    Evidence Purified perlecan binding assays on HS-deficient cells, monoclonal antibody inhibition, rabbit ear angiogenesis model

    PMID:7528102

    Open questions at the time
    • Identity of the minimal HS structure required for ternary complex formation was not defined
    • Whether perlecan HS versus other HSPGs had unique or redundant co-receptor function was unresolved
  2. 1997 High

    Genetic loss-of-function confirmed perlecan as the principal endogenous FGF-2 co-receptor, ruling out redundancy with other cell-surface HSPGs, while parallel promoter studies showed TGF-β transcriptionally upregulates perlecan via an NF-1-binding element.

    Evidence Stable antisense suppression in fibroblasts/melanoma with rescue by exogenous perlecan; promoter deletion/EMSA/reporter assays in skin fibroblasts

    PMID:9030592 PMID:9121441

    Open questions at the time
    • In vivo genetic confirmation in mammals was still lacking
    • Which downstream signaling pathways are activated was not yet characterized
  3. 1999 High

    Knockout mice revealed that perlecan is essential for basement membrane integrity under mechanical stress and for cartilage collagen network organization, with the chondrodysplasia phenotype paralleling FGFR3 gain-of-function, placing perlecan in the FGF/FGFR3 signaling axis of chondrogenesis.

    Evidence Two independent Hspg2-null mouse lines with histology, EM, and phenotypic comparison to FGFR3 mutant mice

    PMID:10545953 PMID:10579729

    Open questions at the time
    • Whether perlecan acts through HS chains or protein core in cartilage was unresolved
    • Direct biochemical demonstration of perlecan–FGFR3 interaction was missing
  4. 2000 High

    Domain-mapping studies revealed that the perlecan protein core (domains III and V) binds FGF-7 independently of heparan sulfate, and that perlecan mediates a distinct lipoprotein internalization/degradation pathway via β1 integrins, while in vivo vascular studies showed perlecan prevents thrombosis after deep injury.

    Evidence Yeast two-hybrid/radioligand binding for FGF-7; pharmacological dissection of lipoprotein endocytosis; antisense-perlecan endothelial cells in porcine carotid artery model

    PMID:10702276 PMID:10818109 PMID:10841569

    Open questions at the time
    • Whether FGF-7 core-protein binding activates FGFR2 signaling was not yet shown genetically
    • The integrin subtype mediating lipoprotein uptake was not identified
  5. 2001 High

    Genetic disruption of HSPG2 in colon carcinoma cells demonstrated that the protein core — not HS chains — is required for functional KGF/FGFR2-IIIb receptor activation, while perlecan-null ES cells revealed its requirement for laminin matrix organization through a dystroglycan–β1 integrin axis, and domain III was shown to bind FGF-BP.

    Evidence Targeted homologous recombination in colon carcinoma cells with signaling assays; perlecan-null ES cell laminin clustering; yeast two-hybrid/co-IP for FGF-BP

    PMID:11148217 PMID:11228157 PMID:11563979

    Open questions at the time
    • Structural basis for core-protein-mediated FGFR2 activation was unknown
    • Whether FGF-BP–perlecan interaction modulates FGF activity in vivo was untested
  6. 2003 High

    Perlecan was shown to modulate Hedgehog signaling in addition to FGF in Drosophila neuroblast proliferation, its HS chains were identified as heparanase substrates relevant to tumor invasion, progranulin was identified as a domain V ligand with antagonistic growth effects, and HS-specific domain I deletion in mice revealed tissue-specific roles in lens capsule integrity versus glomerular filtration.

    Evidence Drosophila trol genetic epistasis with Hh/FGF pathways and Co-IP; in vitro heparanase digestion of purified perlecan; yeast two-hybrid/SPR for progranulin–domain V; Hspg2 exon 3 deletion mouse

    PMID:12514129 PMID:12645928 PMID:12900424 PMID:14630925

    Open questions at the time
    • Whether perlecan directly binds Hh in mammals in vivo was not confirmed
    • Tissue-specific HS chain functions beyond lens and kidney were uncharacterized
  7. 2005 High

    Multiple studies converged on perlecan's role in neuromuscular junction biology and epithelial survival: domain V/LG domains promote AChR clustering through MuSK-dependent laminin polymerization, a trimolecular dystroglycan–laminin–perlecan complex was demonstrated, HS chains on SMC-derived perlecan suppress intimal hyperplasia by sequestering FGF-2, and perlecan is essential for keratinocyte survival through FGF-7 bioavailability.

    Evidence AChR clustering assays with MuSK phosphorylation; solid-phase trimolecular binding and Large(myd) mouse; Hspg2Δ3/Δ3 mice in flow cessation model; perlecan siRNA in organotypic skin with FGF-7 rescue

    PMID:14739157 PMID:15872080 PMID:16098969 PMID:16219760 PMID:16269412

    Open questions at the time
    • Whether domain V alone is sufficient for NMJ formation in vivo was untested
    • The precise signaling pathway downstream of perlecan mediating keratinocyte survival was incompletely defined
  8. 2006 High

    The chondroitin sulfate chains of cartilage perlecan — specifically 4,6-disulfated CS-E — were shown to directly accelerate collagen II fibril formation, providing a mechanistic explanation for the disorganized collagen network in perlecan-null cartilage independent of growth factor signaling.

    Evidence In vitro collagen fibril formation assay with purified perlecan, chondroitinase treatment, GAG compositional analysis, EM

    PMID:16956876

    Open questions at the time
    • Whether CS-E on perlecan is the dominant collagen-organizing signal in vivo versus other CS proteoglycans was unresolved
    • Regulation of CS sulfation on perlecan was not addressed
  9. 2007 High

    Perlecan core protein domain III was mapped as an FGF-18 binding site that antagonizes FGF-18 mitogenic activity in chondrocytes, revealing that perlecan can both promote and inhibit FGF signaling depending on the ligand and domain involved.

    Evidence Cationic filtration, immunoprecipitation, enzymatic treatment of GAG chains, recombinant domain expression, thymidine incorporation

    PMID:17971291

    Open questions at the time
    • Whether this antagonism operates in vivo at growth plate FGF-18 concentrations was not shown
    • Whether domain III simultaneously binds FGF-7 and FGF-18 was unresolved
  10. 2008 High

    Zebrafish perlecan depletion demonstrated that domain V/endorepellin mediates the majority of perlecan's biological activities in muscle development and angiogenic vessel sprouting, as domain V injection alone rescued both myopathy and vascular defects.

    Evidence Morpholino knockdown with domain V protein rescue microinjection, live imaging of actin and vasculature

    PMID:18426981

    Open questions at the time
    • Receptor(s) mediating domain V angiogenic rescue in zebrafish were not identified
    • Whether domain V is processed from full-length perlecan in vivo was not demonstrated
  11. 2012 High

    Drosophila genetic epistasis placed perlecan in the Sema-1a/PlexA repulsive axon guidance pathway, where it facilitates semaphorin signaling by antagonizing integrin/FAK activity, extending perlecan's role from growth factor co-receptor to semaphorin signaling modulator.

    Evidence Drosophila double/triple mutant analysis of trol, Sema-1a, PlexA, integrin, FAK; phospho-FAK assay in insect cells

    PMID:23028146

    Open questions at the time
    • Whether mammalian perlecan similarly modulates semaphorin signaling was unconfirmed at this time
    • Direct physical interaction between perlecan and Sema-1a was not demonstrated
  12. 2014 High

    A series of studies revealed MMP-7 cleavage of perlecan domain IV as a molecular switch: intact domain IV-3 binds Sema3A to deactivate FAK and promote cell clustering, while MMP-7 processing destroys this complex and activates FAK-driven invasion; cell-type-specific GAG decoration was shown to determine FGF signaling selectivity; and domain II O-linked sialylated glycans were identified as a novel LDL retention mechanism.

    Evidence In vitro MMP-7 digestion with cell invasion/clustering assays and FAK readout; Sema3A co-IP and siRNA; cell-type-specific perlecan GAG analysis; solid-phase binding with MS glycan analysis for domain II–LDL

    PMID:24509440 PMID:24833109 PMID:25528754 PMID:29740048

    Open questions at the time
    • Whether MMP-7 cleavage of perlecan occurs during metastasis in vivo was not shown
    • Identity of the sialylated O-glycan structures on domain II was not fully elucidated
  13. 2015 High

    Perlecan was established as a regulator of vascular tone and pulmonary vascular remodeling: HS chains form the FGF2–FGFR1 ternary complex required for hypoxic PASMC proliferation and pulmonary hypertension, while perlecan deficiency reduces eNOS expression to impair endothelium-dependent relaxation; biophysical measurements showed the full-length core protein is a ~170 nm monomeric rod capable of withstanding >100 pN force.

    Evidence Hspg2Δ3/Δ3 mice in hypoxia PH model with LACE assay; conditional perlecan KO with aortic ring relaxation; AFM imaging and single-molecule force spectroscopy

    PMID:25626871 PMID:25952902 PMID:26546708

    Open questions at the time
    • Whether perlecan mechanically transmits force to osteocytes in the lacunar-canalicular system was not yet functionally tested
    • Upstream mechanism of perlecan regulation of eNOS transcription was unknown
  14. 2019 Medium

    Perlecan was identified as a functional component of the pro-metastatic cancer-associated fibroblast niche and as a mechanosensory transducer in osteocytes: stromal perlecan depletion enhances chemotherapy efficacy, while perlecan-deficient osteocytes show impaired calcium signaling with downregulation of ryanodine receptor and SERCA pathways.

    Evidence Intravital imaging with stromal perlecan depletion and survival analysis in pancreatic cancer model; real-time Ca2+ imaging in loaded murine tibiae with RNA-seq

    PMID:31406163 PMID:31715337

    Open questions at the time
    • Mechanism by which perlecan in the stroma modulates drug resistance was not fully elucidated
    • Whether perlecan directly interacts with Ryr1/Atp2a1 or regulates them transcriptionally was unclear
    • The pro-metastatic stroma study defined upstream p53 dependency only partially
  15. 2024 High

    Perlecan haploinsufficiency in human cardiomyocytes was shown to impair structural maturation and force generation via the dystroglycan complex, with perlecan peptide substrate rescuing hypertrophic growth, establishing perlecan as a critical cardiomyocyte maturation factor signaling through dystroglycan.

    Evidence HSPG2+/- hPSC-derived cardiomyocytes, engineered heart tissue contractility, perlecan peptide substrate culture, dystroglycan interaction assessment

    PMID:38198277

    Open questions at the time
    • Which specific dystroglycan-complex subunit mediates the perlecan maturation signal was not defined
    • Whether this mechanism is relevant to human cardiomyopathy in vivo remains untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for perlecan core-protein-mediated receptor activation, whether in vivo MMP-7 processing of perlecan drives metastatic dissemination, the mechanism linking perlecan to eNOS transcription, and whether perlecan functions as a direct mechanotransducer in bone.
  • No atomic-resolution structure of any full domain–ligand complex exists
  • In vivo evidence for MMP-7 cleavage of perlecan during cancer progression is lacking
  • Direct force-transmission function in the osteocyte lacunar-canalicular system has not been reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 2
Localization
GO:0031012 extracellular matrix 5 GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-109582 Hemostasis 1
Partners
DAG1FGF2FGFBP1FGFR1GRNLAMA1MMP7SEMA3A
Complex memberships
HS–FGF–FGFR ternary complexdystroglycan complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Perlecan induces high-affinity binding of bFGF (FGF-2) to cells deficient in heparan sulfate and to soluble FGF receptors, functioning as a major accessory/co-receptor for bFGF; monoclonal antibodies to perlecan block this receptor-binding-promoting activity; perlecan potently induces bFGF-mediated neovascularization in vivo. Affinity-purified HSPG binding assays, monoclonal antibody inhibition, in vivo rabbit ear angiogenesis model Cell High 7528102
1997 Stable antisense suppression of perlecan in NIH 3T3 fibroblasts and melanoma cells dramatically reduces high-affinity bFGF receptor binding and mitogenic response, which can be rescued by exogenous heparin or perlecan, confirming perlecan as a major bFGF accessory receptor in vivo. Antisense cDNA stable transfection, Northern blot, immunoblot, 125I-bFGF receptor binding/affinity labeling, thymidine incorporation proliferation assay Molecular and cellular biology High 9121441
1999 Homozygous perlecan (Hspg2) null mice develop normally formed basement membranes initially, but BMs deteriorate under mechanical stress (contracting myocardium, expanding brain vesicles), causing cardiac blood leakage, exencephaly, and severe chondrodysplasia with disorganized fibrillar collagen network, demonstrating perlecan is essential for BM integrity and cartilage ECM maintenance. Gene knockout mouse, electron microscopy, histology, immunohistochemistry, collagen ECM gene expression analysis The Journal of cell biology High 10579729
1999 Hspg2-/- mice exhibit severe skeletal dysplasia with disorganized chondrocyte columnar structures, reduced collagen fibrils and glycosaminoglycans in cartilage matrix, reduced chondrocyte proliferation, and diminished prehypertrophic zone, phenotypically similar to thanatophoric dysplasia caused by activating FGFR3 mutations, placing perlecan in the FGF/FGFR3 signaling axis regulating chondrogenesis. Hspg2 gene disruption in mice, histology, immunostaining, comparison with Fgfr3 gain-of-function mouse phenotype (genetic epistasis inference) Nature genetics High 10545953
2000 The protein core of perlecan binds FGF-7 (KGF) specifically to the N-terminal half of domain III and to domain V, with affinity constants ~60 nM, independent of heparan sulfate chains; this interaction is demonstrated by overlay protein assays, radioligand binding, and yeast two-hybrid. Overlay protein assays, radioligand binding experiments, yeast two-hybrid system The Journal of biological chemistry High 10702276
2000 Perlecan mediates internalization and lysosomal delivery of atherogenic lipoproteins enriched in lipoprotein lipase via a kinetically and biochemically distinct pathway from coated pits or syndecan-mediated endocytosis; binding is blocked by heparitinase, degradation by chloroquine, and internalization is inhibited by genistein but not cytochalasin D; beta1 integrins serve as cell-surface attachment sites for perlecan. Cell-based binding, internalization and degradation assays using cells expressing perlecan but no other proteoglycans; pharmacological inhibitors; antibody blockade The Journal of biological chemistry High 10818109
2001 Perlecan domain III interacts with FGF-binding protein (FGF-BP) at the second EGF repeat; this interaction was identified by yeast two-hybrid, confirmed by co-immunoprecipitation and solid-phase binding to recombinant domain III-alkaline phosphatase fusion protein, and they co-localize in tumor stroma in vivo. Yeast two-hybrid, co-immunoprecipitation, solid-phase binding, immunohistochemistry The Journal of biological chemistry High 11148217
2001 In perlecan-null ES cells, complex laminin-1 matrix structures fail to form, and laminin and perlecan reciprocally modulate each other's organization on the cell surface; beta1 integrin function is required downstream of dystroglycan for laminin matrix assembly. Null-mutant ES cell lines (perlecan-deficient, beta1 integrin-deficient, dystroglycan-deficient), laminin clustering assays, fluorescence microscopy Journal of cell science High 11228157
2001 Perlecan protein core (not heparan sulfate chains) is required for functional activation of the KGF receptor (FGFR2-IIIb) and downstream signaling in colon carcinoma cells; perlecan-deficient cells (via targeted homologous recombination) do not respond to FGF7, and heparin cannot substitute for perlecan in this signaling context. Targeted homologous recombination to disrupt HSPG2, KGF receptor signaling assays, growth assays, FGF7 surface binding The Biochemical journal High 11563979
2003 Perlecan (encoded by trol) regulates neuroblast division in Drosophila by modulating both FGF and Hedgehog signaling; human FGF-2 rescues trol mutant proliferation phenotype; Trol co-immunoprecipitates with Hh and mammalian perlecan with Shh (not competed by heparan sulfate); trol affects Hh movement through tissue, placing perlecan upstream of both FGF/MAPK and Hh pathways. Drosophila trol mutant genetic analysis, FGF-2 rescue in culture, co-immunoprecipitation, MAPK inhibitor assays, genetic epistasis (trol, hh, ttv mutations) Developmental biology High 12645928
2003 Perlecan co-immunoprecipitates with CTGF/Hcs24 from chondrocytes; CTGF stimulates perlecan gene expression; CTGF effects on chondrocyte aggrecan expression and DNA/proteoglycan synthesis are abolished by heparinase pretreatment, demonstrating that CTGF signals through heparan sulfate proteoglycans including perlecan to regulate chondrocyte proliferation and differentiation. Immunofluorescence co-localization, Northern blot, in vitro co-immunoprecipitation, 125I-rCTGF binding, heparinase inhibition of CTGF-stimulated gene expression Journal of cellular physiology Medium 12811819
2003 Heparanase (HPSE-1) specifically degrades heparan sulfate chains of purified perlecan (as well as syndecan-1); cell-surface syndecan-1 inhibits HPSE-1-mediated invasion of melanoma cells in a manner requiring its HS chains, revealing perlecan as a degradative substrate of heparanase with implications for tumor invasion. In vitro enzymatic digestion of purified HSPGs, in vitro chemoinvasion assays, pharmacological/HS-chain-dependent inhibition experiments The Journal of biological chemistry High 14630925
2003 Progranulin binds specifically to perlecan domain V (first two laminin- and EGF-like repeats interacting with granulins F and B) with KD ~1 µM; both progranulin and domain V individually stimulate adrenal carcinoma cell growth, but equimolar combination antagonizes each other's activity. Yeast two-hybrid, co-immunoprecipitation (cell-free transcription/translation and transient transfection), surface plasmon resonance The Journal of biological chemistry High 12900424
2003 Perlecan-null cartilage shows reduced collagen fibril density not attributable to increased gelatinase (MMP-2/MMP-9) activity; crossing perlecan null onto MMP-9 null background fails to rescue cartilage ultrastructural abnormalities, ruling out MMP-9 as the primary effector of collagen loss. Genetic cross of perlecan-null and MMP-9-null mice, immunohistochemistry, in situ and SDS-PAGE zymography Annals of the New York Academy of Sciences Medium 12814946
2003 Perlecan heparan sulfate chains of exon 3 (domain I) are indispensable for lens capsule integrity but not required for kidney glomerular filtration under normal conditions; deletion of HS attachment sites causes lens apoptosis, cellular membrane leakage, and lens degeneration; glomerular HS charge density is maintained by chondroitin sulfate compensation in mutant mice. Hspg2 exon 3 deletion mouse (HS-deficient perlecan), electron microscopy, apoptosis assay, urinalysis, immunostaining The EMBO journal High 12514129
2004 Perlecan heparan sulfate (HS) side chains of smooth muscle cell perlecan suppress SMC proliferation; HS-deficient perlecan transgenic mice show increased SMC proliferation and enhanced intimal hyperplasia after carotid artery flow cessation; HS-deficient perlecan shows defective ECM-binding capacity for FGF-2. Transgenic mice with HS-deficient perlecan (Hspg2Δ3/Δ3), flow cessation carotid artery model, SMC culture proliferation assays, FGF-2 ECM-binding assay Circulation research High 14739157
2005 Heparan sulfate chains of perlecan in domain I contribute to glomerular filtration of protein; Hspg2Δ3/Δ3 mice exhibit remarkable proteinuria when protein-loaded, despite no baseline structural abnormality; mutant perlecan is partially substituted with chondroitin sulfate instead, maintaining charge density under basal conditions. Hspg2Δ3/Δ3 mouse, BSA challenge intraperitoneal injection, urinary protein measurement, polyethyleneimine charge staining, immunostaining, transcript analysis Journal of the American Society of Nephrology High 15872080
2005 Epidermally derived perlecan (not dermal) is essential for keratinocyte survival and stratification during epidermal formation; perlecan-deficient keratinocytes show premature apoptosis and fail stratification; exogenous perlecan restores epidermal formation; FGF-7 partially rescues perlecan-deficient keratinocytes from cell death, suggesting perlecan regulates FGF-7 bioavailability. Perlecan siRNA knockdown in engineered human skin (organotypic coculture), rescue with exogenous perlecan or FGF-7, apoptosis assays, immunostaining The Journal of biological chemistry High 16269412
2006 Cartilage perlecan bearing chondroitin sulfate chains (specifically 4,6-disulfated chondroitin sulfate E) binds collagen and accelerates collagen type II fibril formation in vitro, producing more defined fibril morphology and increased fibril diameters; this enhancement is glycosaminoglycan- (not core protein-) dependent and is mimicked by chondroitin sulfate E but not chondroitin sulfate D. In vitro collagen fibril formation assay with purified perlecan, chondroitinase treatment, GAG disaccharide compositional analysis, electron microscopy of fibrils The Journal of biological chemistry High 16956876
2007 The perlecan core protein (not HS or CS chains) binds FGF-18 via cysteine-rich regions of domain III with KD ~27.8–145 nM; perlecan reverses FGF-18-stimulated chondrocyte proliferation, acting as an antagonist of FGF-18 mitogenic activity in growth plate chondrocytes. Cationic filtration and immunoprecipitation binding assays, chondroitinase/heparitinase treatment, reduction/alkylation of core protein, recombinant domain expression, 3H-thymidine incorporation Archives of biochemistry and biophysics High 17971291
2008 Perlecan depletion in zebrafish causes severe myopathy with abnormal actin filament orientation and disorganized sarcomeres, and failure of primary intersegmental vessel sprouts to extend; phenotype is partially rescued by injection of human perlecan or its C-terminal domain V/endorepellin, demonstrating endorepellin mediates most biological activities of perlecan in muscle and angiogenesis. Morpholino-based protein depletion in zebrafish, protein rescue microinjection, live videomicroscopy, fluorescence imaging of actin and vasculature The Journal of cell biology High 18426981
2000 Perlecan is required to prevent thrombosis after deep vascular injury; antisense-perlecan endothelial cells fail to prevent occlusive thrombosis in a porcine carotid artery model; perlecan suppression reduces endothelial cell ability to inhibit FGF-2 binding and mitogenic activity in smooth muscle cells, while only partially abrogating intimal hyperplasia suppression. Antisense perlecan vector in endothelial cells, three-dimensional polymeric matrix implantation in porcine carotid artery deep injury model, FGF-2 binding and mitogenesis assays Proceedings of the National Academy of Sciences of the United States of America High 10841569
1998 Perlecan binds alpha-dystroglycan in a calcium- and heparin-sensitive manner (blot overlay assay and co-immunoprecipitation); cell-surface perlecan co-localizes with dystroglycan at AChR clusters in Xenopus muscle cells; perlecan and dystroglycan are co-clustered at ACh receptor clusters induced by spinal neurons or HB-GAM-coated beads, suggesting perlecan is anchored to the muscle surface via the DG-dystrophin complex. Blot overlay assay, co-immunoprecipitation with anti-DG antibody, immunofluorescence co-localization in Xenopus muscle cells Cell adhesion and communication Medium 9791728
2005 Laminin polymerization promotes perlecan assembly on cell surfaces; dystroglycan, laminin, and perlecan form a trimolecular complex demonstrated by solid-phase binding; LARGE-deficient (glycosylation-deficient) mice show reduced perlecan-binding activity and perlecan mislocalization, linking dystroglycan glycosylation to perlecan matrix assembly. Solid-phase ligand binding assays (trimolecular complex), cell-surface ligand clustering assays, analysis of Large(myd) mouse FEBS letters Medium 16098969
2005 Perlecan LG domains (domain V) promote AChR clustering in the presence of laminin-2 through a MuSK-dependent mechanism requiring laminin polymerization; perlecan-LG-dependent AChR clustering is accompanied by tyrosine phosphorylation of MuSK and betaAChR; antibody-mediated aggregation of non-neural agrin mimics this clustering, supporting a ligand-aggregation mechanism. Myotube culture AChR clustering assay, MuSK inhibition, tyrosine phosphorylation western blot, antibody crosslinking experiments The Journal of biological chemistry Medium 16219760
2012 Drosophila perlecan (trol) is required for Sema-1a/PlexA-mediated repulsive motor axon guidance; trol mutations suppress Sema-1a-mediated defasciculation phenotypes; perlecan augments the reduction of phospho-FAK induced by Sema-1a in insect cells; genetic interactions among integrin, Sema-1a, and FAK indicate perlecan facilitates Sema-1a signaling by antagonizing integrin/FAK activity. Drosophila genetic epistasis (trol, Sema-1a, PlexA, integrin, FAK double/triple mutants), in vitro phospho-FAK assay in insect cells, perlecan rescue in mutant motor neurons Genes & development High 23028146
2013 Perlecan is required for FGF-2 signaling in the adult subventricular zone neurogenic niche; perlecan deficiency reduces neural stem cells (GFAP/CD133+) and new neurons; in the absence of perlecan, FGF-2 fails to promote neurosphere formation and fails to activate Akt and Erk1/2 or induce cyclin D2 expression. Perlecan-deficient mouse, neurosphere formation assay, FGF-2 stimulation with Akt/Erk1/2 pathway readout, cyclin D2 expression, immunostaining for neural stem cell markers Stem cell research High 24434631
2014 MMP-7 (matrilysin) cleaves perlecan specifically at domain IV immunoglobulin repeat regions even when perlecan is fully HS-decorated or embedded in native basement membrane context; a C-terminal domain IV fragment (Dm IV-3) induces PCa cell clustering via FAK dephosphorylation/deactivation; MMP-7 cleavage reverses clustering to cell dispersion with FAK activation, acting as a molecular switch for cancer cell invasion. In vitro MMP-7 digestion of purified perlecan, recombinant domain IV fragments, Transwell invasion assay, cell clustering phenotype assays, comparison with PSA, hepsin, FAP enzymes Matrix biology : journal of the International Society for Matrix Biology High 24833109
2014 Smooth muscle cell-derived perlecan contains both HS and CS chains, whereas endothelial cell-derived perlecan contains exclusively HS; SMC perlecan binds FGF1 and FGF2 via HS but promotes only FGF2 signaling, while endothelial perlecan promotes both FGF1 and FGF2 signaling; SMC adhesion to perlecan core requires GAG removal and involves a novel domain III site and domain V/endorepellin via alpha2beta1 integrin. Isolation and GAG characterization of cell-type-specific perlecan, FGF binding assays, signaling assays, integrin-blocking antibodies, cell adhesion assays Matrix biology : journal of the International Society for Matrix Biology High 24509440
2014 Perlecan domain IV-3 binds semaphorin 3A (Sema3A) on PCa cells (demonstrated by direct binding experiments and co-IP); this perlecan-Sema3A complex deactivates FAK and promotes PCa cell clustering (tumoroid formation); MMP-7 cleaves both perlecan and Sema3A, destroying the complex and activating FAK to drive cell dispersion and invasion. Direct binding experiments, co-immunoprecipitation, Sema3A antibody mimicry, siRNA knockdown of Sema3A, MMP-7 cleavage assays, FAK phosphorylation western blot, Transwell invasion Scientific reports High 29740048
2015 Perlecan deficiency in endothelial cells (siRNA knockdown) or in a conditional perlecan knockout mouse reduces eNOS gene and protein expression, resulting in impaired acetylcholine-dependent endothelium-dependent relaxation while preserving nitroprusside (NO donor)-dependent relaxation. Conditional perlecan-deficient mouse, isolated aortic ring isometric force measurements, real-time PCR, Western blot, siRNA knockdown in human aortic endothelial cells Physiological reports High 25626871
2015 Perlecan HS chains (domain I) are required for formation of the HS-FGF2-FGFR1 ternary complex; Hspg2Δ3/Δ3 mice show impaired FGFR1 phosphorylation and reduced PASMC proliferation in response to hypoxia, attenuating pulmonary hypertension development. Hspg2Δ3/Δ3 mice, hypoxia PH model, ligand and carbohydrate engagement (LACE) assay for ternary complex formation, FGFR1 phosphorylation western blot, PASMC proliferation assay, selective FGFR1 inhibition Cardiovascular research High 25952902
2015 Perlecan/HSPG2 core protein is a monomeric rod of 170±20 nm end-to-end length (measured by AFM), capable of withstanding >100 pN tensile force (elastic constant 890 pN, Young's modulus 71 MPa), physically suitable to span the osteocyte pericellular space and act as a mechanical tether in the lacunar-canalicular system. Atomic force microscopy imaging and single-molecule force measurements (SMFM) of purified full-length human perlecan, extensible worm-like chain model fitting Matrix biology : journal of the International Society for Matrix Biology High 26546708
1997 TGF-beta transcriptionally induces perlecan mRNA and protein 2-3 fold in skin fibroblasts via a NF-1-binding element located between -461 and -285 bp in the promoter; TNF-alpha has no effect and cannot counteract TGF-beta; the TGF-beta responsive element binds TGF-beta-inducible nuclear proteins with high affinity. Transient cell transfection reporter assays, 5' deletion and internal deletion analysis, DNase footprinting, electrophoretic mobility shift assays (EMSA), mutational analyses, Northern blot/protein quantification The Journal of biological chemistry High 9030592
2014 TNF-alpha is a major cytokine regulator of perlecan production via NF-kappaB; TNF-alpha triggers p65 nuclear translocation and binding to the HSPG2 regulatory region containing conserved NF-kappaB binding sites; reporter construct dissection locates an active cis-element in the distal HSPG2 promoter region. HSPG2 promoter reporter construct transfections with systematic deletions, cytokine treatment, p65 nuclear translocation assay, chromatin-level p65 binding Journal of cellular biochemistry Medium 24700612
2014 Perlecan domain II core protein interacts with LDL via O-linked sialylated glycans; sialic acid residues on domain II are critical for LDL binding; HS and domain II have an additive effect on LDL binding; unlike LDLR (which mediates endocytosis), perlecan DII mediates receptor-mediated lipoprotein retention in the arterial wall. Solid-phase binding assays, glycan analysis of secreted DII (MS), sialic acid-specific inhibition, domain-specific binding experiments Journal of lipid research High 25528754
2019 Perlecan is a key component of the pro-metastatic CAF environment driven by GOF mutant p53 cancer cells; depletion of perlecan from the stroma combined with chemotherapy prolongs mouse survival; perlecan depletion reduces chemotherapy resistance in a pancreatic cancer model observed by intravital imaging. Intravital imaging, perlecan stromal depletion (genetic/RNAi), combination with chemotherapy in mouse model, survival analysis with mechanistic framing Nature communications Medium 31406163
2019 Perlecan deficiency (Hypo mice) impairs osteocyte calcium signaling in response to mechanical loading; perlecan-deficient osteocytes show reduced Ca2+ response rate, peak magnitude, and recovery; RNA sequencing identifies suppression of calcium signaling, ECM-receptor interaction, and focal adhesion pathways, with defects in Ryr1 and Atp2a1 (ER calcium cycling regulators). Real-time Ca2+ imaging in situ in murine tibiae under cyclic loading, RNA sequencing, pathway analysis Bone Medium 31715337
2024 Perlecan haploinsufficiency in hPSC-derived cardiomyocytes causes structural immaturity (reduced alpha-actinin), increased glycolytic metabolism, and proliferation; perlecan-haploinsufficient engineered heart tissues have reduced thickness and force generation; hPSC-CMs grown on perlecan peptide substrate are enlarged with increased nucleation (hypertrophic growth); perlecan signaling is mediated via the dystroglycan complex. HSPG2+/- hPSC haploinsufficiency, cardiomyocyte differentiation, engineered heart tissue force measurement, perlecan peptide substrate culture, dystroglycan complex interaction assessment Cell reports High 38198277
2011 Perlecan co-localizes with elastin and fibrillin-1 in connective tissues; tropoelastin interacts with perlecan heparan sulfate chains (quartz crystal microbalance), and core protein also contributes; this interaction promotes tropoelastin coacervation and deposition of elastin onto perlecan, supporting elastic microfibril assembly. Immunohistochemistry co-localization, quartz crystal microbalance with dissipation (QCM-D) solid-phase binding, heparan sulfate-dependent interaction analysis Histochemistry and cell biology Medium 21874555
2002 Type XIII collagen ectodomain binds perlecan (and fibronectin, nidogen-2, heparin) with nanomolar KD values determined by surface plasmon resonance; binding sites for nidogen-2 and perlecan reside in pepsin-sensitive non-collagenous portions of type XIII collagen. Surface plasmon resonance binding assay, pepsin digestion domain mapping The Journal of biological chemistry Medium 11956183
2023 TNFSF13 binds HSPG2/perlecan on hypertrophic scar fibroblasts; the TNFSF13/HSPG2 interaction activates NF-kappaB signaling to promote fibroblast proliferation, migration, fibrosis, and inflammation; silencing HSPG2 or inhibiting NF-kappaB eliminates TNFSF13 pro-fibrotic effects; MSC-derived exosomes suppress TNFSF13 and HSPG2 to reduce fibroblast activity. Recombinant TNFSF13 protein treatment, TNFSF13/HSPG2 siRNA knockdown, protein-protein binding assays, NF-kappaB pathway inhibition, CCK-8/EdU/Transwell assays, western blot International journal of nanomedicine Medium 38046235

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Perlecan maintains the integrity of cartilage and some basement membranes. The Journal of cell biology 513 10579729
1994 Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis. Cell 476 7528102
1999 Perlecan is essential for cartilage and cephalic development. Nature genetics 411 10545953
2019 CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nature communications 215 31406163
2008 Diverse cell signaling events modulated by perlecan. Biochemistry 214 18826258
2003 Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. The EMBO journal 180 12514129
2016 A current view of perlecan in physiology and pathology: A mosaic of functions. Matrix biology : journal of the International Society for Matrix Biology 162 27613501
1997 Developmental expression of perlecan during murine embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 159 9337134
2013 Skin basement membrane: the foundation of epidermal integrity--BM functions and diverse roles of bridging molecules nidogen and perlecan. BioMed research international 140 23586018
1998 The relationship between perlecan and dystroglycan and its implication in the formation of the neuromuscular junction. Cell adhesion and communication 139 9791728
2003 Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division. Developmental biology 131 12645928
2001 Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization. Journal of cell science 131 11228157
2000 The protein core of the proteoglycan perlecan binds specifically to fibroblast growth factor-7. The Journal of biological chemistry 124 10702276
2001 Fibroblast growth factor-binding protein is a novel partner for perlecan protein core. The Journal of biological chemistry 120 11148217
2013 Border patrol: insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders. Matrix biology : journal of the International Society for Matrix Biology 118 24001398
1995 Perlecan is a component of cartilage matrix and promotes chondrocyte attachment. Journal of cell science 118 7593307
2020 Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan. Frontiers in oncology 117 32010611
2003 Heparanase degrades syndecan-1 and perlecan heparan sulfate: functional implications for tumor cell invasion. The Journal of biological chemistry 115 14630925
2003 A novel interaction between perlecan protein core and progranulin: potential effects on tumor growth. The Journal of biological chemistry 114 12900424
2000 Perlecan is required to inhibit thrombosis after deep vascular injury and contributes to endothelial cell-mediated inhibition of intimal hyperplasia. Proceedings of the National Academy of Sciences of the United States of America 114 10841569
1993 Structural characterization of the complete human perlecan gene and its promoter. Proceedings of the National Academy of Sciences of the United States of America 114 8234307
1994 Abnormal expression of perlecan proteoglycan in metastatic melanomas. Cancer research 112 7954396
2014 The role of vascular-derived perlecan in modulating cell adhesion, proliferation and growth factor signaling. Matrix biology : journal of the International Society for Matrix Biology 110 24509440
2013 The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2). The Journal of biological chemistry 102 23436656
2008 A central function for perlecan in skeletal muscle and cardiovascular development. The Journal of cell biology 99 18426981
1997 Suppression of autocrine and paracrine functions of basic fibroblast growth factor by stable expression of perlecan antisense cDNA. Molecular and cellular biology 98 9121441
2000 Perlecan heparan sulfate proteoglycan: a novel receptor that mediates a distinct pathway for ligand catabolism. The Journal of biological chemistry 97 10818109
2002 Accumulation of biglycan and perlecan, but not versican, in lesions of murine models of atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 96 11884291
1997 Structural and functional characterization of the human perlecan gene promoter. Transcriptional activation by transforming growth factor-beta via a nuclear factor 1-binding element. The Journal of biological chemistry 92 9030592
2003 CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes. Journal of cellular physiology 84 12811819
2006 Chondroitin sulfate perlecan enhances collagen fibril formation. Implications for perlecan chondrodysplasias. The Journal of biological chemistry 82 16956876
2022 Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration. Frontiers in cell and developmental biology 80 35433700
2005 Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermal formation. The Journal of biological chemistry 80 16269412
2005 Heparan sulfate of perlecan is involved in glomerular filtration. Journal of the American Society of Nephrology : JASN 79 15872080
2004 Increased intimal hyperplasia and smooth muscle cell proliferation in transgenic mice with heparan sulfate-deficient perlecan. Circulation research 79 14739157
2008 Novel interactions of perlecan: unraveling perlecan's role in angiogenesis. Microscopy research and technique 78 18300285
2002 The type XIII collagen ectodomain is a 150-nm rod and capable of binding to fibronectin, nidogen-2, perlecan, and heparin. The Journal of biological chemistry 78 11956183
2006 Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome. Human mutation 76 16927315
2000 Perlecan domain V of Drosophila melanogaster. Sequence, recombinant analysis and tissue expression. European journal of biochemistry 76 10824099
2000 Identification and immunolocalization of decorin, versican, perlecan, nidogen, and chondroitin sulfate proteoglycans in bovine small-antral ovarian follicles. Biology of reproduction 76 10952939
2004 The role of perlecan in arterial injury and angiogenesis. Cardiovascular research 74 15306215
1997 A role for perlecan in the suppression of growth and invasion in fibrosarcoma cells. Cancer research 73 9187109
2013 Perlecan is required for FGF-2 signaling in the neural stem cell niche. Stem cell research 66 24434631
1997 Expression of heparan sulfate proteoglycan (perlecan) in the mouse blastocyst is regulated during normal and delayed implantation. Developmental biology 66 9142982
2018 Modular Proteoglycan Perlecan/HSPG2: Mutations, Phenotypes, and Functions. Genes 63 30453502
2014 Matrilysin/matrix metalloproteinase-7(MMP7) cleavage of perlecan/HSPG2 creates a molecular switch to alter prostate cancer cell behavior. Matrix biology : journal of the International Society for Matrix Biology 62 24833109
1995 Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence. The Journal of biological chemistry 55 7814401
2009 The modulation of platelet and endothelial cell adhesion to vascular graft materials by perlecan. Biomaterials 54 19540587
2006 Chondrogenic differentiation on perlecan domain I, collagen II, and bone morphogenetic protein-2-based matrices. Tissue engineering 53 16889529
2021 Perlecan in Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation and Mechanoregulation of Load-Bearing Connective Tissues. International journal of molecular sciences 50 33800241
2002 Role of perlecan in skeletal development and diseases. Glycoconjugate journal 50 12975604
2001 Dyssegmental dysplasia, Silverman-Handmaker type: unexpected role of perlecan in cartilage development. American journal of medical genetics 50 11891676
2000 Lipoprotein modulation of subendothelial heparan sulfate proteoglycans (perlecan) and atherogenicity. Trends in cardiovascular medicine 50 11150731
2018 The multifaceted roles of perlecan in fibrosis. Matrix biology : journal of the International Society for Matrix Biology 49 29475023
2012 The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance. Genes & development 49 23028146
2014 Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma. PloS one 46 25506919
2005 Disruption of perlecan binding and matrix assembly by post-translational or genetic disruption of dystroglycan function. FEBS letters 46 16098969
1996 Purification and characterization of perlecan fragment in urine of end-stage renal failure patients. Clinica chimica acta; international journal of clinical chemistry 46 8937755
2011 Colocalization in vivo and association in vitro of perlecan and elastin. Histochemistry and cell biology 45 21874555
2014 Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis. G3 (Bethesda, Md.) 44 25504735
2010 Association of the HSPG2 gene with neuroleptic-induced tardive dyskinesia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 43 20072119
2007 The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts. BMC developmental biology 41 17980035
2004 Atherosclerosis in perlecan heterozygous mice. Journal of lipid research 41 15258195
2003 Role of collagen type II and perlecan in skeletal development. Annals of the New York Academy of Sciences 41 12814946
2007 A novel peptide sequence in perlecan domain IV supports cell adhesion, spreading and FAK activation. Matrix biology : journal of the International Society for Matrix Biology 40 17997086
2007 The core protein of growth plate perlecan binds FGF-18 and alters its mitogenic effect on chondrocytes. Archives of biochemistry and biophysics 39 17971291
2015 Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix. Matrix biology : journal of the International Society for Matrix Biology 38 26546708
2019 Discovery of HSPG2 (Perlecan) as a Therapeutic Target in Triple Negative Breast Cancer. Scientific reports 37 31462656
2014 Drosophila perlecan regulates intestinal stem cell activity via cell-matrix attachment. Stem cell reports 37 24936464
2009 Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro. Tissue engineering. Part A 37 19382872
2005 Perlecan displays variable spatial and temporal immunolocalisation patterns in the articular and growth plate cartilages of the ovine stifle joint. Histochemistry and cell biology 36 16021525
2018 Matrilysin/MMP-7 Cleavage of Perlecan/HSPG2 Complexed with Semaphorin 3A Supports FAK-Mediated Stromal Invasion by Prostate Cancer Cells. Scientific reports 35 29740048
2014 Transcriptional activation by NFκB increases perlecan/HSPG2 expression in the desmoplastic prostate tumor microenvironment. Journal of cellular biochemistry 35 24700612
2001 UNC-52/perlecan isoform diversity and function in Caenorhabditis elegans. Biochemical Society transactions 35 11356148
2016 Perlecan expression influences the keratin 15-positive cell population fate in the epidermis of aging skin. Aging 34 26996820
2003 Large matrix proteoglycans, versican and perlecan, are expressed and secreted by human leukemic monocytes. Anticancer research 34 12926067
2015 Perlecan heparan sulfate deficiency impairs pulmonary vascular development and attenuates hypoxic pulmonary hypertension. Cardiovascular research 32 25952902
2001 Perlecan inhibits smooth muscle cell adhesion to fibronectin: role of heparan sulfate. Journal of cellular physiology 32 11382923
1996 Structural and cell-adhesive properties of three recombinant fragments derived from perlecan domain III. Matrix biology : journal of the International Society for Matrix Biology 32 8981331
2018 IL-1 and TGF-β Modulation of Epithelial Basement Membrane Components Perlecan and Nidogen Production by Corneal Stromal Cells. Investigative ophthalmology & visual science 31 30480706
2016 Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc. European cells & materials 31 27377666
2001 A role for the perlecan protein core in the activation of the keratinocyte growth factor receptor. The Biochemical journal 31 11563979
2015 Perlecan deficiency causes endothelial dysfunction by reducing the expression of endothelial nitric oxide synthase. Physiological reports 29 25626871
2012 Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and osteogenesis. BMC biotechnology 29 22967000
1995 Expression of the basement membrane heparan sulfate proteoglycan (perlecan) in human synovium and in cultured human synovial cells. Laboratory investigation; a journal of technical methods and pathology 29 7474938
2017 The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin. Matrix biology : journal of the International Society for Matrix Biology 27 28433812
2014 Anionic biopolyelectrolytes of the syndecan/perlecan superfamily: physicochemical properties and medical significance. Advances in colloid and interface science 27 24534475
2014 Perlecan antagonizes collagen IV and ADAMTS9/GON-1 in restricting the growth of presynaptic boutons. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 25080592
2021 Stem cell niche organization in the Drosophila ovary requires the ECM component Perlecan. Current biology : CB 26 33621481
2006 Reduced perlecan expression and accumulation in human carotid atherosclerotic lesions. Atherosclerosis 26 16620836
2005 Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering. The Journal of biological chemistry 26 16219760
2004 Perlecan functions in chondrogenesis: insights from in vitro and in vivo models. Cells, tissues, organs 26 14745237
2015 Differential expression of epithelial basement membrane components nidogens and perlecan in corneal stromal cells in vitro. Molecular vision 25 26788024
2014 The glycosylation-dependent interaction of perlecan core protein with LDL: implications for atherosclerosis. Journal of lipid research 25 25528754
2019 Perlecan/Hspg2 deficiency impairs bone's calcium signaling and associated transcriptome in response to mechanical loading. Bone 23 31715337
2023 Exosome Derived from Mesenchymal Stem Cells Alleviates Hypertrophic Scar by Inhibiting the Fibroblasts via TNFSF-13/HSPG2 Signaling Pathway. International journal of nanomedicine 22 38046235
2020 SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models. PloS one 22 32413029
2014 NGS nominated CELA1, HSPG2, and KCNK5 as candidate genes for predisposition to Balkan endemic nephropathy. BioMed research international 22 24949484
2005 Altered perlecan expression in placental development and gestational diabetes mellitus. Placenta 22 16226129
2024 Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes. Cell reports 21 38198277