Affinage

HSPG2

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

Length
4391 aa
Mass
468.8 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Perlecan (HSPG2) is a large modular heparan sulfate proteoglycan built from five distinct protein-core domains—an HS-attachment domain I, an LDL-receptor-like domain II, a laminin-like domain III, a domain IV of immunoglobulin repeats, and a laminin G-like domain V—that organizes basement membranes and pericellular matrices and modulates growth-factor signaling (PMID:1569102). Its HS chains act as accessory co-receptors that potentiate FGF and VEGF signaling: perlecan promotes high-affinity bFGF–receptor binding and bFGF-driven angiogenesis (PMID:7528102), its HS is required to assemble the HS–FGF2–FGFR1 ternary complex (PMID:25952902), and it binds VEGF-A165 to enhance VEGFR2 activation during developmental angiogenesis (PMID:19422911). Beyond its glycan chains, the perlecan protein core itself transduces signals, being required for KGF/FGFR2 activation independently of HS (PMID:11563979) and supporting integrin-mediated cell adhesion through a domain III RGDS site and a domain IV immunoglobulin-repeat peptide that drives FAK activation (PMID:7814401, PMID:17997086). Structurally, perlecan maintains basement membrane and cartilage integrity under mechanical stress, with null mice showing stress-induced BM deterioration, cardiac failure, exencephaly, and disorganized chondrocyte columns and collagen fibrils (PMID:10579729, PMID:10545953), phenotypes mirrored in humans where HSPG2 mutations cause Schwartz-Jampel syndrome (myotonia with skeletal dysplasia) (PMID:11101850) and functional-null mutations cause lethal dyssegmental dysplasia Silverman-Handmaker type (PMID:11891676). In muscle, perlecan anchors to the cell surface via alpha-dystroglycan and organizes the neuromuscular junction (PMID:9791728), and regulates fast muscle mass through myostatin signaling (PMID:20541011). Domain V (endorepellin) engages alpha5beta1 integrin to drive pericyte and stem-cell behaviors (PMID:32947020, PMID:24936464), while MMP-7 cleavage of domain IV acts as a molecular switch—disrupting domain IV-3/Sema3A-mediated FAK deactivation to convert prostate cancer cells from cohesion to invasion (PMID:24833109, PMID:29740048).

Mechanistic history

Synthesis pass · year-by-year structured walk · 31 steps
  1. 1992 High

    Establishing the five-domain modular architecture of the perlecan core defined the structural basis for its multifunctionality, assigning candidate functions to each domain (HS attachment, LDL-receptor homology, laminin/NCAM-like adhesion modules).

    Evidence cDNA cloning and full-length sequence determination with in situ hybridization and immunolocalization

    PMID:1569102

    Open questions at the time
    • Domain-level functions inferred from homology, not yet functionally tested
    • No structural model of the assembled core
  2. 1993 High

    Complete genomic mapping correlated 94 exons to protein domains and revealed a TATA-less, SP1/ETF promoter, indicating constitutive housekeeping-style regulation.

    Evidence Intron-exon mapping and promoter characterization from genomic DNA

    PMID:8234307

    Open questions at the time
    • Cell-type-specific and inducible regulation not addressed
    • Alternative splicing of functional variants not catalogued
  3. 1994 High

    Identifying perlecan as a low-affinity/accessory bFGF receptor that potentiates mitogenesis and neovascularization assigned its HS chains a direct role in growth-factor signaling rather than purely structural support.

    Evidence Receptor binding on HS-deficient cells, neutralizing antibodies, in vivo rabbit ear angiogenesis

    PMID:7528102

    Open questions at the time
    • Ternary complex stoichiometry not resolved at the time
    • Did not distinguish HS- vs core-dependent contributions
  4. 1995 High

    Demonstrating that domain III supports RGDS-dependent integrin adhesion established the protein core (not just HS) as a direct cell-adhesion substrate.

    Evidence Recombinant domain III adhesion assays with RGDS peptide inhibition

    PMID:7814401

    Open questions at the time
    • Specific integrin heterodimer not pinned down
    • Downstream signaling not characterized
  5. 1996 High

    C. elegans unc-52 work showed perlecan is a cell-autonomous muscle ECM product essential for myofilament assembly and muscle attachment, linking the proteoglycan to muscle architecture.

    Evidence unc-52 genetic analysis, antibody labeling, laser ablation in C. elegans

    PMID:8575624

    Open questions at the time
    • Molecular receptor mediating attachment not identified in worm
    • Mammalian conservation of mechanism untested here
  6. 1998 Medium

    Identifying alpha-dystroglycan as a calcium/heparin-sensitive perlecan partner provided a surface-anchoring mechanism linking perlecan to the DG-dystrophin complex and AChR clustering at the NMJ.

    Evidence Blot overlay, co-IP, and immunofluorescence in Xenopus muscle

    PMID:9791728

    Open questions at the time
    • Binding domain on perlecan not mapped
    • Limited mechanistic follow-up beyond single lab
  7. 1999 High

    Two independent knockouts established perlecan as essential for stress-resistant basement membranes and cartilage matrix integrity, with the chondrocyte phenotype resembling FGFR3 gain-of-function and implicating shared signaling.

    Evidence Hspg2-null mouse histology, EM, BrdU proliferation, GAG analysis

    PMID:10545953 PMID:10579729

    Open questions at the time
    • Whether BM failure is purely mechanical vs signaling-driven not separated
    • FGFR3 epistasis was inferential, not direct
  8. 1999 Medium

    Perlecan substrates were shown to drive chondrogenic differentiation of mesenchymal cells, indicating an instructive, not merely scaffolding, role in cartilage formation.

    Evidence Culture of 10T1/2 cells on purified perlecan with chondrogenic marker readouts

    PMID:10352025

    Open questions at the time
    • Receptor/signal mediating differentiation not identified
    • Single lab, in vitro only
  9. 2000 High

    Human SJS1 mutation discovery established HSPG2 as a disease gene controlling both cartilage integrity and muscle excitability, validating the mouse phenotypes in humans.

    Evidence Mutation sequencing and linkage in SJS1 families

    PMID:11101850

    Open questions at the time
    • Mechanism linking perlecan loss to myotonia not resolved
    • Genotype-phenotype relationships incomplete
  10. 2000 Medium

    A perlecan-only cell system revealed a distinct beta1-integrin-dependent endocytic pathway for atherogenic lipoprotein uptake and degradation, expanding perlecan's role into lipid handling.

    Evidence Lipoprotein binding/internalization/degradation assays with inhibitors and integrin/LRP blockade

    PMID:10818109

    Open questions at the time
    • In vivo relevance to atherosclerosis untested
    • Molecular machinery of the pathway incompletely defined
  11. 2001 High

    Genetic disruption in human carcinoma cells showed the perlecan protein core, not its HS chains, is required for KGF/FGFR2 activation, distinguishing core-dependent from HS-dependent growth-factor functions.

    Evidence Targeted HSPG2 knockout colon carcinoma cells with FGF7 binding/activation assays and heparin controls

    PMID:11563979

    Open questions at the time
    • Core domain mediating FGFR2 activation not localized
    • Direct core-FGF7 binding not demonstrated
  12. 2001 Medium

    Mapping FGF-binding protein to a specific EGF repeat in domain III provided a molecular basis for perlecan core participation in FGF signaling in tumor stroma.

    Evidence Yeast two-hybrid, co-IP, recombinant domain III-AP binding, IHC in squamous carcinoma

    PMID:11148217

    Open questions at the time
    • Functional consequence of the interaction in vivo unproven
    • Single lab
  13. 2002 High

    DDSH mutation work showed functional-null perlecan that is unstable and unsecreted causes lethal dwarfism, demonstrating that secretion into the ECM is essential for cartilage development.

    Evidence HSPG2 mutation identification with tissue immunostaining and secretion analysis in DDSH patients

    PMID:11891676

    Open questions at the time
    • Cellular quality-control pathway retaining mutant protein not defined here
    • Relationship to milder SJS allelic series unresolved at the time
  14. 2003 High

    Drosophila trol work placed perlecan as a modulator of both FGF and Hedgehog signaling in neuroblast division, with direct perlecan-Shh binding not competed by heparin, indicating core-mediated Hh interaction.

    Evidence trol genetics, FGF-2 rescue, MAPK inhibition, Trol/Hh and Perlecan/Shh co-IP

    PMID:12645928

    Open questions at the time
    • Perlecan domain binding Hh not mapped
    • Mammalian Shh modulation tested only biochemically
  15. 2003 Medium

    Domain V was shown to bind ECM1 and progranulin, with the progranulin interaction functionally counteracting domain V's growth-promoting activity, establishing domain V as a hub for partner-modulated signaling.

    Evidence Yeast two-hybrid, co-IP, SPR kinetics, cell growth assays

    PMID:12604605 PMID:12900424

    Open questions at the time
    • In vivo significance of these interactions untested
    • Single lab for each interaction
  16. 2003 Medium

    Heparanase was shown to specifically degrade perlecan HS chains, linking perlecan HS turnover to tumor cell invasion.

    Evidence In vitro HPSE-1 digestion of purified perlecan HS and chemoinvasion assays

    PMID:14630925

    Open questions at the time
    • Released HS fragment activities not characterized
    • In vivo invasion link correlative
  17. 2007 Medium

    A domain IV TWSKVGG peptide was shown to drive cation-independent, heparin-sensitive adhesion and FAK activation, adding a distinct adhesion module to the perlecan core.

    Evidence Peptide adhesion/spreading assays with FAK activation across cell lines

    PMID:17997086

    Open questions at the time
    • Receptor mediating peptide adhesion not identified
    • Relevance of peptide to intact perlecan unproven
  18. 2006 Medium

    Distinguishing mutation classes in SJS established hypomorphic mechanisms—NMD for truncating alleles and intracellular retention for cysteine missense alleles—explaining graded disease severity.

    Evidence mRNA and immunostaining analysis of 22 new mutations in SJS patient cells

    PMID:16927315

    Open questions at the time
    • Quality-control machinery retaining missense protein not identified
    • Quantitative dose-phenotype relationships incomplete
  19. 2009 High

    Zebrafish work established perlecan as required for developmental angiogenesis, binding and concentrating VEGF-A165 in an HS-dependent manner to enhance VEGFR2 activation.

    Evidence Morpholino knockdown, VEGF-A binding assay, VEGFR2 phosphorylation, VEGF-A165 mRNA rescue

    PMID:19422911

    Open questions at the time
    • Whether perlecan core also contributes to VEGF signaling not addressed
    • Endothelial vs matrix source of perlecan not separated
  20. 2010 Medium

    Perlecan deficiency was shown to cause fast-fiber muscle hypertrophy via reduced myostatin/ALK4-Smad signaling, defining a role in muscle mass regulation distinct from its structural functions.

    Evidence Hspg2(-/-)-Tg mouse fiber analysis and myotube Smad activation assays

    PMID:20541011

    Open questions at the time
    • Direct perlecan-myostatin binding not demonstrated
    • Single lab
  21. 2011 Medium

    Localization to the osteocyte lacunocanalicular system and tropoelastin binding established perlecan as a pericellular structural organizer supporting interstitial fluid spaces and elastogenesis.

    Evidence Immunogold/TEM ultrastructure in KO bone; QCM-D tropoelastin binding with tissue co-localization

    PMID:20814969 PMID:21874555

    Open questions at the time
    • Functional consequence for bone mechanotransduction not yet linked here
    • Tropoelastin binding determinants only partially mapped
  22. 2012 High

    Drosophila trol was shown to modulate Sema-1a/PlexA repulsive axon guidance via phospho-FAK regulation, revealing ECM proteoglycan tuning of transmembrane guidance-cue signaling.

    Evidence trol genetics with Sema-1a/PlexA, in vitro phospho-FAK assays, motor-neuron-specific rescue

    PMID:23028146

    Open questions at the time
    • Direct perlecan-Sema/Plexin binding not shown in fly
    • Mammalian conservation untested here
  23. 2013 Medium

    Perlecan was established as a neural stem cell niche component required for FGF-2-dependent self-renewal via Akt/Erk and cyclin D2 activation.

    Evidence Hspg2-null mouse SVZ analysis and neurosphere/FGF-2 signaling assays

    PMID:24434631

    Open questions at the time
    • Whether HS or core mediates the niche effect not separated
    • Single lab
  24. 2014 Medium

    A series of studies dissected cell-type-specific perlecan glycosylation, domain V/alpha5beta1 stem-cell niche function, TNF-alpha/NF-kappaB transcriptional control, and domain II glycan-dependent LDL retention, refining how perlecan composition tailors its function.

    Evidence SMC/EC perlecan isolation and GAG analysis; Drosophila ISC genetics; HSPG2 promoter ChIP; recombinant domain II LDL binding

    PMID:24509440 PMID:24700612 PMID:24936464 PMID:25528754

    Open questions at the time
    • In vivo integration of these context-specific functions incomplete
    • Each finding from a single lab
  25. 2014 High

    Identifying MMP-7 cleavage of domain IV as a molecular switch from clustering (anti-invasive) to dispersion (pro-invasive) defined a regulated mechanism converting perlecan from cohesion to invasion-permissive.

    Evidence In vitro MMP-7 digestion of perlecan, recombinant domain IV subdomains, invasion and clustering assays

    PMID:24833109

    Open questions at the time
    • In vivo demonstration of the switch limited
    • Receptor for intact domain IV-3 clustering not yet identified here
  26. 2015 High

    HS-specific knockouts and domain V studies dissected perlecan HS as essential for the HS-FGF2-FGFR1 ternary complex in pulmonary vascular remodeling, while domain V/alpha5beta1 promotes PDGF-driven pericyte migration and perlecan suppresses muscle autophagy via mTORC1.

    Evidence Hspg2(Δ3/Δ3) HS-deficient mice with LACE assay; recombinant domain V pericyte signaling; KO muscle autophagy pathway analysis

    PMID:25952902 PMID:26319110 PMID:32947020

    Open questions at the time
    • Crosstalk between HS-dependent and core-dependent functions not unified
    • Domain V pericyte mechanism from single lab
  27. 2016 Medium

    Perlecan HS chains were shown to organize type VI collagen pericellularly and stabilize intervertebral disc matrix, extending its pericellular structural role to translamellar cross-bridges.

    Evidence SPR binding and HS-deficient mouse cross-bridge quantification

    PMID:27377666

    Open questions at the time
    • Mechanism by which HS organizes collagen VI not detailed
    • Single lab
  28. 2018 Medium

    Domain IV-3 was shown to bind Sema3A directly to deactivate FAK and stabilize tumor cell-cell interactions, with MMP-7 cleavage disrupting the complex—mechanistically explaining the cohesion-to-invasion switch.

    Evidence Direct binding, Sema3A antibody/siRNA, FAK phosphorylation, tumoroid assays, MMP-7 digestion

    PMID:29740048

    Open questions at the time
    • In vivo prostate cancer relevance not established here
    • Single lab
  29. 2019 Medium

    Perlecan deficiency was shown to impair osteocyte calcium signaling under mechanical load, with transcriptomic suppression of calcium signaling, ECM-receptor, and focal adhesion pathways, defining a mechanosensory role in bone.

    Evidence In situ real-time Ca2+ imaging in loaded tibiae and RNA-seq in KO mice

    PMID:31715337

    Open questions at the time
    • Direct link between pericellular perlecan and Ca2+ machinery not mechanistically resolved
    • Single lab
  30. 2023 Medium

    TNFSF13 was shown to bind cell-surface HSPG2 to activate NF-kappaB and drive fibroblast proliferation/fibrosis, identifying perlecan as a co-receptor in hypertrophic scar pathology.

    Evidence Co-binding assay, HSPG2 siRNA, NF-kappaB inhibition, proliferation/migration assays

    PMID:38046235

    Open questions at the time
    • Binding domain on perlecan not mapped
    • In vivo scar model not tested
  31. 2024 Medium

    Perlecan haploinsufficiency was shown to impair cardiomyocyte structural, contractile, and metabolic maturation via the dystroglycan complex, extending its role to cardiac tissue maturation.

    Evidence HSPG2+/- hPSC-CM and engineered heart tissue assays with peptide substrate and dystroglycan interaction studies

    PMID:38198277

    Open questions at the time
    • Specific perlecan domain driving maturation not pinned down
    • Single lab; human in vitro model only

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how perlecan's distinct functional modules—HS-dependent growth-factor co-receptor activity, core-protein integrin/adhesion signaling, and dystroglycan anchoring—are integrated and prioritized in a given tissue context, and which receptor mediates several core-domain effects (KGF/FGFR2 activation, domain IV peptide adhesion, domain IV-3 clustering).
  • No unified structural model of the assembled five-domain core with bound partners
  • Receptors for several core-domain functions remain unidentified
  • Tissue-specific division of labor between HS and core not systematically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098772 molecular function regulator activity 4 GO:0098631 cell adhesion mediator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3 GO:0030312 external encapsulating structure 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 2
Partners
COL6DAG1ECM1FGF2FGFBP1GRNSEMA3AVEGFA
Complex memberships
HS-FGF2-FGFR1 ternary complexdystroglycan-dystrophin complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Human perlecan (HSPG2) protein core is composed of five distinct domains: domain I (unique, contains Ser-Gly-Asp heparan sulfate attachment sites), domain II (homologous to LDL receptor with cysteine repeats), domain III (homologous to laminin A chain short arm), domain IV (21 immunoglobulin-type repeats similar to NCAM), and domain V (homologous to laminin A G-domain with EGF-like repeats), establishing the modular architecture of the protein. cDNA cloning, sequencing of 18 overlapping clones covering 14.35 kb, deduced amino acid sequence analysis, in situ hybridization, immunoenzymatic studies The Journal of biological chemistry High 1569102
1993 The HSPG2 gene spans >120 kbp and is composed of 94 exons, with each exon assigned to modular protein domains; the promoter lacks canonical TATA or CAAT boxes but contains SP1 and ETF binding sites with multiple transcription initiation sites, consistent with a housekeeping gene regulation pattern. Complete intron-exon mapping by genomic DNA analysis, promoter characterization, sequencing Proceedings of the National Academy of Sciences of the United States of America High 8234307
1994 Perlecan promotes high-affinity binding of bFGF (FGF-2) to its receptor on cells deficient in heparan sulfate and to soluble FGF receptors, augments heparin-dependent mitogenic activity of bFGF, and potently induces bFGF-mediated neovascularization in vivo, identifying perlecan as a major accessory/low-affinity receptor for bFGF and an angiogenic modulator. Affinity-purified HSPG binding assays, receptor binding assays on HS-deficient cells, neutralizing monoclonal antibodies, in vivo rabbit ear angiogenesis model, mitogenesis assays Cell High 7528102
1995 Recombinant perlecan domain III supports integrin-mediated cell attachment via its RGDS sequence; adhesion is specifically inhibited by RGDS peptide and intact perlecan but not laminin, demonstrating a role for perlecan domain III in integrin-mediated signaling. Recombinant domain III expression and purification, cell adhesion assays on coated dishes, inhibition with synthetic RGDS peptide, rotary shadow electron microscopy The Journal of biological chemistry High 7814401
1996 Perlecan is a cell-autonomous product of muscle cells in C. elegans (encoded by unc-52) and is essential for myofilament formation and muscle attachment; perlecan expressed in individual muscle cells does not spread beyond the borders of the ECM underlying that cell, demonstrating cell-autonomous ECM function. Genetic analysis of unc-52 mutants, polyclonal antibody labeling, laser ablation of blastomeres, immunofluorescence during C. elegans development Developmental biology High 8575624
1998 Perlecan binds alpha-dystroglycan (alpha-DG) in a calcium- and heparin-sensitive manner; perlecan co-localizes with dystroglycan at cell surfaces of Xenopus muscle cells, is co-immunoprecipitated with anti-DG antibody from muscle lysate, and clusters at ACh receptor clusters at the neuromuscular junction, suggesting perlecan is anchored to muscle surface via the DG-dystrophin complex. Blot overlay assays, co-immunoprecipitation, immunofluorescence co-localization in Xenopus muscle cells, AChR clustering assays Cell adhesion and communication Medium 9791728
1999 Perlecan null mice show normal basement membrane (BM) formation initially, but BMs deteriorate under mechanical stress (contracting myocardium, expanding brain vesicles), leading to cardiac failure and exencephaly; perlecan-null cartilage shows reduced fibrillar collagen network and shortened fibers with elevated ECM gene expression, demonstrating perlecan maintains BM integrity and protects cartilage ECM from degradation. Homozygous null mutation (gene knockout) in mice, histology, electron microscopy, immunohistochemistry, Northern blotting The Journal of cell biology High 10579729
1999 Hspg2-null mice show severe disorganization of chondrocyte columnar structures, defective endochondral ossification, reduced and disorganized collagen fibrils and glycosaminoglycans in cartilage matrix, reduced chondrocyte proliferation, and diminished prehypertrophic zone, demonstrating perlecan is essential for cartilage matrix structure and chondrocyte proliferation. Abnormal phenotypes resemble FGFR3 gain-of-function, suggesting perlecan and FGFR3 affect similar signaling pathways. Gene disruption (Hspg2 knockout) in mice, histology, electron microscopy, BrdU proliferation assay, glycosaminoglycan analysis, immunostaining Nature genetics High 10545953
1999 Culture on perlecan (but not other matrices including fibronectin, laminin, or collagen) stimulates multipotential mesenchymal fibroblasts (10T1/2) to form dense nodules with Alcian blue staining and collagen type II expression, and elevates mRNAs for collagen II, aggrecan, and perlecan itself, demonstrating perlecan promotes chondrogenic differentiation in vitro. Cell culture on purified perlecan substrates, Alcian blue staining, immunostaining for collagen II, Northern blotting for chondrogenic markers The Journal of cell biology Medium 10352025
2000 Cells expressing perlecan (but no other proteoglycans) bind, internalize, and degrade atherogenic lipoproteins enriched in lipoprotein lipase via a pathway kinetically and biochemically distinct from coated-pit or syndecan-mediated endocytosis; binding is blocked by heparitinase, degradation by chloroquine, internalization inhibited by genistein but not cytochalasin D, and beta1 integrins serve as cell surface attachment sites for perlecan. Lipoprotein binding, internalization, and degradation assays in cells expressing only perlecan; pharmacological inhibitors; antibody blockade of beta1 integrin and LRP The Journal of biological chemistry Medium 10818109
2000 Mutations (missense and splicing) in HSPG2 cause Schwartz-Jampel syndrome (SJS1), a rare autosomal recessive disorder with permanent myotonia and skeletal dysplasia, establishing perlecan as essential for both maintaining cartilage integrity and regulating muscle excitability in humans. Mutation identification by sequencing in SJS1 families, linkage to chromosome 1p34-p36.1 Nature genetics High 11101850
2001 The perlecan protein core (not its heparan sulfate chains) is required for functional activation of the KGF receptor (FGFR2/KGF-R) and downstream signaling in colon carcinoma cells; perlecan-deficient cells (generated by targeted homologous recombination) fail to respond to FGF7 even with added heparin, though they show increased FGF7 surface binding. Targeted homologous recombination to generate perlecan-null colon carcinoma cells, FGF7 binding assays, cell proliferation assays, receptor activation assays, heparin supplementation controls The Biochemical journal High 11563979
2001 FGF-binding protein (FGF-BP) interacts specifically with the protein core of perlecan domain III (second EGF repeat), as identified by yeast two-hybrid screening and validated by co-immunoprecipitation and binding to recombinant domain III-alkaline phosphatase fusion protein; FGF-BP and perlecan co-localize in the pericellular stroma of squamous cell carcinomas. Yeast two-hybrid screen of keratinocyte cDNA library, deletion mutant mapping, co-immunoprecipitation, recombinant domain III-alkaline phosphatase fusion binding assay, immunohistochemistry The Journal of biological chemistry Medium 11148217
2001 Dyssegmental dysplasia Silverman-Handmaker type (DDSH), a lethal form of dwarfism, is caused by functional null mutations of HSPG2; insertion and splicing mutations create premature termination codons, the mutant perlecan is unstable and not secreted into the extracellular matrix, demonstrating perlecan is essential for cartilage development in humans. HSPG2 mutation identification in DDSH patients, immunostaining of patient tissue, biochemical analysis of perlecan secretion American journal of medical genetics High 11891676
2003 Perlecan protein core interacts with extracellular matrix protein 1 (ECM1) through its domain V; specifically, the C-terminus of ECM1 binds the EGF-like modules flanking the LG2 subdomain of perlecan domain V, as validated by yeast two-hybrid, co-immunoprecipitation in cell-free systems and mammalian cells, and deletion mutant mapping. Yeast two-hybrid screen, co-immunoprecipitation in cell-free and mammalian cell systems, deletion mutant binding mapping, identification of novel ECM1c splice variant The Journal of biological chemistry Medium 12604605
2003 Progranulin (a secreted growth factor) interacts with perlecan domain V through the first two laminin- and EGF-like repeats, binding to granulin F and B subdomains, with a KD ~1 μM measured by surface plasmon resonance; both progranulin and domain V individually stimulate adrenal carcinoma cell growth, but together in equimolar amounts counteract each other's activity. Yeast two-hybrid, co-immunoprecipitation in cell-free and transfected mammalian cells, surface plasmon resonance kinetics, cell growth assays, tumor tissue microarrays The Journal of biological chemistry Medium 12900424
2003 Heparanase (HPSE-1) specifically degrades the heparan sulfate chains of purified perlecan, as demonstrated with purified syndecan-1 and perlecan HS; perlecan HS is thus a degradative substrate of heparanase, with functional implications for tumor cell invasion. In vitro enzymatic degradation of purified syndecan-1 and perlecan HS with HPSE-1, in vitro chemoinvasion assays, cell surface HS degradation assays The Journal of biological chemistry Medium 14630925
2003 Drosophila perlecan (encoded by trol) regulates neuroblast division by modulating both FGF and Hedgehog (Hh) signaling; FGF-2 addition rescues trol proliferation phenotype, MAPK inhibitor blocks wild-type neuroblast division, Hh activates stem cell division in a Trol-dependent fashion, and co-immunoprecipitation shows interactions between Trol and Hh and between mammalian Perlecan and Sonic Hedgehog that are not competed by heparin sulfate. Drosophila genetic analysis (trol mutants), brain culture rescue with human FGF-2, MAPK inhibitor treatment, co-immunoprecipitation of Trol/Hh and Perlecan/Shh, genetic epistasis of trol/hh/ttv Developmental biology High 12645928
2006 HSPG2 mutations causing SJS show a hypomorphic effect; truncating mutations cause HSPG2 mRNA instability via nonsense-mediated mRNA decay, whereas missense mutations involving cysteine residues cause intracellular retention of perlecan, likely through quality control pathways, establishing distinct molecular consequences of different mutation classes. HSPG2 mRNA analysis, perlecan immunostaining on patient cells, sequencing of 22 new mutations in 23 SJS families Human mutation Medium 16927315
2007 A peptide sequence (TWSKVGGHLRPGIVQSG) from an immunoglobulin repeat in perlecan domain IV supports rapid cell adhesion, spreading, and focal adhesion kinase (FAK) activation in a divalent cation-independent, heparin-sensitive manner; cell adhesion is receptor-specific and differs between cell lines. Bioinformatics-based peptide identification, cell adhesion assays, focal adhesion and actin cytoskeleton visualization, FAK activation assays Matrix biology : journal of the International Society for Matrix Biology Medium 17997086
2009 Perlecan is required for proper endothelial cell migration and proliferation during developmental angiogenesis; perlecan knockdown causes abnormal increase and redistribution of total VEGF-A protein, perlecan binds VEGF-A165 in a heparan sulfate-dependent manner, and perlecan enhances VEGF-mediated VEGFR2 activation of human endothelial cells; the morphant phenotype is rescued by VEGF-A165 microinjection. Zebrafish perlecan morpholino knockdown, endothelial cell behavior analysis, VEGF-A localization by immunostaining, VEGF-A/perlecan binding assay (heparan sulfate dependence), VEGFR2 phosphorylation assays in human endothelial cells, mRNA rescue experiments Matrix biology : journal of the International Society for Matrix Biology High 19422911
2010 Perlecan deficiency in skeletal muscle (Hspg2(-/-)-Tg mice) causes muscle hypertrophy with increased type IIb fiber cross-sectional area, substantially decreased myostatin and its type I receptor (ALK4) expression, reduced myostatin-induced Smad activation in myotubes, and altered fiber composition including increased type IIx fibers, demonstrating perlecan regulates fast muscle mass and fiber composition through myostatin signaling. Perlecan-deficient mouse model (Hspg2(-/-)-Tg), fiber cross-sectional area measurements, myosin heavy chain fiber typing, myostatin and ALK4 expression analysis, Smad activation assay in cultured myotubes, tenotomy overload/unload experiments Matrix biology : journal of the International Society for Matrix Biology Medium 20541011
2011 Perlecan/Hspg2 localizes to the osteocyte lacunocanalicular system of cortical bone; perlecan deficiency results in diminished canalicular pericellular area, reduced canalicular density, and fewer transverse tethering elements per canaliculus, demonstrating perlecan maintains the pericellular space of the lacunocanalicular system for interstitial fluid movement. Immunofluorescence, immunogold/TEM localization, ultrastructural measurements by electron microscopy in perlecan-deficient mice Journal of bone and mineral research Medium 20814969
2011 Perlecan HS chains interact with tropoelastin electrostatically through heparan sulfate and core protein; these interactions promote tropoelastin coacervation and deposition of elastin onto immobilized perlecan, demonstrated by quartz crystal microbalance with dissipation studies, with co-localization of elastin, fibrillin-1, and perlecan in connective tissues. Quartz crystal microbalance with dissipation (QCM-D) solid-phase binding, co-localization by immunofluorescence in multiple connective tissues Histochemistry and cell biology Medium 21874555
2012 Drosophila perlecan (trol) is required for Sema-1a-PlexA-mediated repulsive axon guidance; trol mutations suppress Sema-1a-mediated motor axon defasciculation, trol genetically interacts with PlexA and Sema-1a, perlecan augments Sema-1a-induced reduction of phospho-FAK in insect cells, and restoring perlecan to mutant motor neurons rescues guidance defects, revealing ECM proteoglycan modulation of transmembrane guidance cue signaling. Drosophila genetic analysis (trol mutants, genetic interactions), in vitro Sema-1a treatment of insect cells with phospho-FAK measurement, rescue experiments by motor neuron-specific perlecan restoration Genes & development High 23028146
2013 Perlecan is required for FGF-2 signaling in the adult neural stem cell niche; perlecan deficiency reduces GFAP/CD133-positive neural stem cells in the SVZ and new neurons in the olfactory bulb; in the absence of perlecan, FGF-2 fails to promote neurosphere formation or activate Akt/Erk1/2 pathways and cyclin D2 expression, demonstrating perlecan is a niche component regulating FGF-2-dependent neural stem cell self-renewal. Hspg2-null mice, immunohistochemistry, neurosphere formation assay, Western blot for Akt/Erk1/2 phosphorylation and cyclin D2, FGF-2 treatment of wild-type and perlecan-deficient cells Stem cell research Medium 24434631
2014 MMP-7 (matrilysin) cleaves perlecan/HSPG2 at multiple sites within domain IV immunoglobulin repeats, even when fully decorated with HS or in native BM context; domain IV-3 fragment induces PCa cell clustering (anti-invasive), whereas MMP-7 digestion of domain IV-3 reverses clustering to favor cell dispersion, acting as a molecular switch altering PCa cell behavior and promoting invasion through perlecan-rich BM. In vitro digestion of purified perlecan with MMP-7 and other proteases, recombinant domain IV subdomains, Transwell invasion assays, PCa cell clustering/dispersion assays with pre-digested BM extract Matrix biology : journal of the International Society for Matrix Biology High 24833109
2014 Perlecan domain V promotes niche function via α5β1 integrin; Drosophila intestinal stem cells (ISCs) that lose Pcan fail to adhere to ECM, lose identity, and fail to proliferate; these defects are cell-autonomous (loss from ISCs but not surrounding cells causes the phenotype) and depend partially on integrin signaling, not EGFR or JAK/STAT pathways. Drosophila genetic analysis with cell-type-specific Pcan knockdown, ISC identity and proliferation assays, epistasis with integrin/EGFR/JAK-STAT pathways Stem cell reports Medium 24936464
2014 Smooth muscle cell-derived perlecan is decorated with both heparan sulfate and chondroitin sulfate, while endothelial cell-derived perlecan contains exclusively heparan sulfate; smooth muscle cells bind the perlecan protein core (domain III and domain V/endorepellin) only when glycosaminoglycans are removed via α2β1 integrin, whereas endothelial cells adhere to perlecan core in the presence of GAGs; perlecan HS from SMCs promotes FGF2 but not FGF1 signaling, while endothelial perlecan promotes both. Isolation of perlecan from primary human coronary artery SMCs and ECs, GAG characterization, cell adhesion assays with GAG-removed perlecan, integrin blocking antibodies, FGF1/FGF2 signaling assays Matrix biology : journal of the International Society for Matrix Biology Medium 24509440
2014 TNF-α activates NF-κB, which binds conserved sites in the distal HSPG2 promoter (2.6 kb upstream) to upregulate perlecan transcription in prostate cancer stromal and cancer cells; TNF-α but not TGFβ1 is identified as the major cytokine regulator of perlecan production, with p65 nuclear translocation and binding to HSPG2 regulatory region confirmed. HSPG2 promoter reporter constructs (up to 2.6 kb), TNF-α and TGFβ1 treatment, p65 nuclear translocation assay, ChIP for p65 binding to HSPG2 promoter region Journal of cellular biochemistry Medium 24700612
2014 Perlecan domain II (LDLR-like domain) interacts with LDL through O-linked glycans present only in secreted DII; the negatively charged sialic acid caps on O-glycans are critical for LDL binding; HS chains and DII have an additive effect on LDL binding; unlike LDLR, this interaction mediates lipoprotein retention rather than endocytosis. Recombinant domain II binding assays, glycan analysis, deglycosylation experiments, surface plasmon resonance or related binding assays, sialic acid dependency assays Journal of lipid research Medium 25528754
2015 Perlecan heparan sulfate chains are required for formation of the HS-FGF2-FGFR1 ternary complex; Hspg2(Δ3/Δ3) mice (HS-deficient) have reduced pericytes and muscularization of pulmonary vessels, attenuated hypoxic pulmonary hypertension with lower FGFR1 phosphorylation and reduced PASMC proliferation; ligand and carbohydrate engagement assay confirmed perlecan HS is required for HS-FGF2-FGFR1 complex formation. Hspg2(Δ3/Δ3) mice (exon 3 deletion, HS-deficient), pulmonary angiography, RVSP measurement, FGFR1 phosphorylation analysis, ligand and carbohydrate engagement assay (LACE), in vitro PASMC proliferation and adhesion assays, FGFR1 inhibitor treatment Cardiovascular research High 25952902
2015 Perlecan deficiency in slow-twitch soleus muscle enhances autophagic activity (increased LC3II, decreased p62), accompanied by reduced phosphorylation of p70S6k and Akt and increased AMPK phosphorylation, suggesting perlecan inhibits autophagy through the mTORC1 pathway in skeletal muscle. Perlecan-deficient mice (Hspg2(-/-)-Tg), mechanical unloading (tenotomy), Western blot for autophagy markers (LC3II, p62), mTORC1 pathway analysis (p70S6k, Akt phosphorylation), AMPKα phosphorylation Matrix biology : journal of the International Society for Matrix Biology Medium 26319110
2015 Perlecan domain V promotes pericyte migration by interacting with α5β1 integrin to enhance PDGF-BB-induced phosphorylation of PDGFRβ, Src homology region 2 domain-containing phosphatase-2 (SHP-2), and focal adhesion kinase (FAK), supporting blood-brain barrier repair after ischemic stroke. Recombinant domain V treatment, phosphorylation assays for PDGFRβ/SHP-2/FAK, integrin α5β1 interaction assays, pericyte migration assays The international journal of biochemistry & cell biology Medium 32947020
2016 Perlecan interacts with type VI collagen pericellularly in intervertebral disc; this interaction is confirmed by surface plasmon resonance; translamellar cross-bridges are significantly less abundant in HS-deficient Hspg2 exon 3 null mice than in wild type, demonstrating perlecan HS chains contribute to type VI collagen pericellular organization and IVD matrix stability. Confocal laser scanning microscopy co-localization, surface plasmon resonance binding assay, Hspg2 exon 3 null mouse (HS-deficient) histology and cross-bridge quantification European cells & materials Medium 27377666
2018 Domain IV-3 of perlecan interacts directly with semaphorin 3A (Sema3A) on prostate cancer cells to deactivate FAK (dephosphorylation) and stabilize cell-cell interactions (tumoroid formation); MMP-7 cleavage of perlecan disrupts the perlecan-Sema3A complex, allowing FAK re-phosphorylation and cell dispersion; Sema3A antibody mimics Domain IV-3 clustering activity and Sema3A knockdown prevents Domain IV-3-induced tumoroid formation. Direct binding experiments (Domain IV-3/Sema3A), Sema3A antibody treatment, Sema3A siRNA knockdown, FAK phosphorylation assays, tumoroid formation assays, MMP-7 digestion of complex Scientific reports Medium 29740048
2019 Perlecan/HSPG2 deficiency impairs osteocyte calcium signaling in response to mechanical loading; perlecan-deficient osteocytes show decreased overall Ca2+ response rate, peaks, and recovery speed; RNA sequencing identifies suppression of calcium signaling, ECM-receptor interaction, and focal adhesion pathways; specific defects in ER calcium cycling regulators (Ryr1/ryanodine receptors and Atp2a1/Serca1 pumps) are identified in Hypo bones. Real-time Ca2+ imaging in situ in murine tibiae under cyclic loading, RNA sequencing with pathway analysis, perlecan-deficient (Hypo) mouse model Bone Medium 31715337
2023 TNFSF13 binds HSPG2 (perlecan) at the cell surface and activates the NF-κB signaling pathway to promote hypertrophic scar fibroblast proliferation, migration, fibrosis, and inflammation; silencing of HSPG2 eliminates the promoting effects of TNFSF13 and inhibition of NF-κB blocks these effects; MSC-derived exosomes reduce TNFSF13 and HSPG2 to inhibit fibroblast activity. Co-binding assay (TNFSF13/HSPG2 interaction), HSPG2 siRNA knockdown, recombinant TNFSF13 protein stimulation, NF-κB inhibition, CCK-8/EdU/Transwell assays, Western blot International journal of nanomedicine Medium 38046235
2024 Perlecan (HSPG2) promotes cardiomyocyte structural, contractile, and metabolic maturation; perlecan-haploinsufficient hPSC-CMs show immature features including reduced α-actinin expression, increased glycolytic metabolism and proliferation; perlecan-haploinsufficient engineered heart tissues have reduced thickness and force generation; hPSC-CMs on perlecan-peptide substrate show hypertrophic growth; perlecan signaling is mediated via the dystroglycan complex. HSPG2+/- hPSC haploinsufficient lines, hPSC-CM differentiation, structural/contractile/metabolic characterization, engineered heart tissue force measurement, perlecan peptide substrate culture, dystroglycan complex interaction assays Cell reports Medium 38198277

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 515 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
1992 Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2/perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. The Journal of biological chemistry 281 1569102
2008 Diverse cell signaling events modulated by perlecan. Biochemistry 214 18826258
2000 Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia). Nature genetics 207 11101850
2016 A current view of perlecan in physiology and pathology: A mosaic of functions. Matrix biology : journal of the International Society for Matrix Biology 164 27613501
1997 Developmental expression of perlecan during murine embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 159 9337134
2003 Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis. The Journal of biological chemistry 152 12604605
2013 Skin basement membrane: the foundation of epidermal integrity--BM functions and diverse roles of bridging molecules nidogen and perlecan. BioMed research international 141 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 132 12645928
1999 Expression of the heparan sulfate proteoglycan, perlecan, during mouse embryogenesis and perlecan chondrogenic activity in vitro. The Journal of cell biology 127 10352025
1994 Perlecan: a gem of a proteoglycan. Matrix biology : journal of the International Society for Matrix Biology 122 7921536
2001 Fibroblast growth factor-binding protein is a novel partner for perlecan protein core. The Journal of biological chemistry 121 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 119 24001398
1995 Perlecan is a component of cartilage matrix and promotes chondrocyte attachment. Journal of cell science 119 7593307
2020 Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan. Frontiers in oncology 118 32010611
2003 Heparanase degrades syndecan-1 and perlecan heparan sulfate: functional implications for tumor cell invasion. The Journal of biological chemistry 115 14630925
2007 Perlecan--a multifunctional extracellular proteoglycan scaffold. Glycobiology 114 17442708
2003 A novel interaction between perlecan protein core and progranulin: potential effects on tumor growth. The Journal of biological chemistry 114 12900424
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
2009 Perlecan regulates developmental angiogenesis by modulating the VEGF-VEGFR2 axis. Matrix biology : journal of the International Society for Matrix Biology 110 19422911
2000 Perlecan heparan sulfate proteoglycan: a novel receptor that mediates a distinct pathway for ligand catabolism. The Journal of biological chemistry 97 10818109
2011 Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 94 20814969
2003 Perlecan and tumor angiogenesis. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 93 14566013
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 82 35433700
2008 Novel interactions of perlecan: unraveling perlecan's role in angiogenesis. Microscopy research and technique 78 18300285
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
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
2018 Single Cell RNA Sequencing Identifies HSPG2 and APLNR as Markers of Endothelial Cell Injury in Systemic Sclerosis Skin. Frontiers in immunology 70 30327649
2013 Perlecan is required for FGF-2 signaling in the neural stem cell niche. Stem cell research 67 24434631
2018 Modular Proteoglycan Perlecan/HSPG2: Mutations, Phenotypes, and Functions. Genes 64 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 63 24833109
2008 Perlecan, the "jack of all trades" proteoglycan of cartilaginous weight-bearing connective tissues. BioEssays : news and reviews in molecular, cellular and developmental biology 62 18404701
2007 Reduced perlecan in mice results in chondrodysplasia resembling Schwartz-Jampel syndrome. Human molecular genetics 60 17213231
1991 Heparan sulfate proteoglycan of human colon: partial molecular cloning, cellular expression, and mapping of the gene (HSPG2) to the short arm of human chromosome 1. Genomics 60 1679749
2015 The role of perlecan and endorepellin in the control of tumor angiogenesis and endothelial cell autophagy. Connective tissue research 59 26181327
2017 Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing. Journal of controlled release : official journal of the Controlled Release Society 55 28189628
1995 Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence. The Journal of biological chemistry 55 7814401
2012 Perlecan and the blood-brain barrier: beneficial proteolysis? Frontiers in pharmacology 54 22936915
2009 The modulation of platelet and endothelial cell adhesion to vascular graft materials by perlecan. Biomaterials 54 19540587
2010 Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition. Matrix biology : journal of the International Society for Matrix Biology 53 20541011
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 51 33800241
2008 Perlecan is critical for heart stability. Cardiovascular research 50 18694874
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
1996 Cell autonomous expression of perlecan and plasticity of cell shape in embryonic muscle of Caenorhabditis elegans. Developmental biology 49 8575624
2020 Perlecan, a modular instructive proteoglycan with diverse functional properties. The international journal of biochemistry & cell biology 48 32947020
2015 Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle. Matrix biology : journal of the International Society for Matrix Biology 47 26319110
2014 Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma. PloS one 47 25506919
2011 Colocalization in vivo and association in vitro of perlecan and elastin. Histochemistry and cell biology 45 21874555
2002 Syndecan-3 and perlecan are differentially expressed by progenitors and mature oligodendrocytes and accumulate in the extracellular matrix. Journal of neuroscience research 45 12210841
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 44 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
1996 Expression of extracellular matrix proteoglycans perlecan and decorin in carbon-tetrachloride-injured rat liver and in isolated liver cells. The American journal of pathology 40 8623917
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
2014 Transcriptional activation by NFκB increases perlecan/HSPG2 expression in the desmoplastic prostate tumor microenvironment. Journal of cellular biochemistry 36 24700612
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
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
2006 Perlecan signaling: helping hedgehog stimulate prostate cancer growth. The international journal of biochemistry & cell biology 33 16750652
2016 Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc. European cells & materials 32 27377666
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
2001 A role for the perlecan protein core in the activation of the keratinocyte growth factor receptor. The Biochemical journal 31 11563979
2012 Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and osteogenesis. BMC biotechnology 29 22967000
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 28 28433812
2012 Perlecan-deficient mutation impairs corneal epithelial structure. Investigative ophthalmology & visual science 28 22266517
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
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
1996 Expression and characterization of human perlecan domains I and II synthesized by baculovirus-infected insect cells. European journal of biochemistry 25 8944771
2023 Exosome Derived from Mesenchymal Stem Cells Alleviates Hypertrophic Scar by Inhibiting the Fibroblasts via TNFSF-13/HSPG2 Signaling Pathway. International journal of nanomedicine 24 38046235
2005 Altered perlecan expression in placental development and gestational diabetes mellitus. Placenta 24 16226129
2019 Perlecan/Hspg2 deficiency impairs bone's calcium signaling and associated transcriptome in response to mechanical loading. Bone 23 31715337
2024 Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes. Cell reports 22 38198277
2011 TGF-β enhances deposition of perlecan from COPD airway smooth muscle. American journal of physiology. Lung cellular and molecular physiology 22 22003087

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