Nidogen: A matrix protein with potential roles in musculoskeletal tissue regeneration

Genes and Diseases - Tập 9 - Trang 598-609 - 2022
Sheng Zhou1, Song Chen2, Yixuan Amy Pei1, Ming Pei1,3
1Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, 26506, USA
2Department of Orthopaedics, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, PR China
3WVU Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA

Tài liệu tham khảo

Pozzi, 2017, The nature and biology of basement membranes, Matrix Biol, 57–58, 1, 10.1016/j.matbio.2016.12.009 Ma, 2017, Basement membrane manipulation in Drosophila wing discs affects Dpp retention but not growth mechanoregulation, Dev Cell, 42, 97, 10.1016/j.devcel.2017.06.004 Wang, 2008, Type IV collagens regulate BMP signalling in Drosophila, Nature, 455, 72, 10.1038/nature07214 Kruegel, 2010, Basement membrane components are key players in specialized extracellular matrices, Cell Mol Life Sci, 67, 2879, 10.1007/s00018-010-0367-x Yurchenco, 2011, Basement membranes: cell scaffoldings and signaling platforms, Cold Spring Harb Perspect Biol, 3, 10.1101/cshperspect.a004911 Kalluri, 2003, Basement membranes: structure, assembly and role in tumour angiogenesis, Nat Rev Canc, 3, 422, 10.1038/nrc1094 Ozbek, 2010, The evolution of extracellular matrix, Mol Biol Cell, 21, 4300, 10.1091/mbc.e10-03-0251 Timpl, 1996, Supramolecular assembly of basement membranes, Bioessays, 18, 123, 10.1002/bies.950180208 Torricelli, 2013, The corneal epithelial basement membrane: structure, function, and disease, Invest Ophthalmol Vis Sci, 54, 6390, 10.1167/iovs.13-12547 Hohenester, 2019, Structural biology of laminins, Essays Biochem, 63, 285, 10.1042/EBC20180075 Hohenester, 2013, Laminins in basement membrane assembly, Cell Adhes Migrat, 7, 56, 10.4161/cam.21831 Yurchenco, 2018, Laminin-deficient muscular dystrophy: molecular pathogenesis and structural repair strategies, Matrix Biol, 71–72, 174, 10.1016/j.matbio.2017.11.009 Yurchenco, 2015, Integrating activities of laminins that drive basement membrane assembly and function, Curr Top Membr, 76, 1, 10.1016/bs.ctm.2015.05.001 Foldager, 2014, Distribution of basement membrane molecules, laminin and collagen type IV, in normal and degenerated cartilage tissues, Cartilage, 5, 123, 10.1177/1947603513518217 Jayadev, 2017, Basement membranes, Curr Biol, 27, R207, 10.1016/j.cub.2017.02.006 Poschl, 2004, Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development, Development, 131, 1619, 10.1242/dev.01037 Brown, 2017, Building collagen IV smart scaffolds on the outside of cells, Protein Sci, 26, 2151, 10.1002/pro.3283 Chioran, 2017, Collagen IV trafficking: the inside-out and beyond story, Dev Biol, 431, 124, 10.1016/j.ydbio.2017.09.037 Njoto, 2019, Modulation of perlecan protein towards chondrocyte secretion factors at the articular cartilage in hyperglycemic animal model, J Pure App Chem Res, 8, 80, 10.21776/ub.jpacr.2019.008.001.450 Sanchez-Adams, 2013, Atomic force microscopy reveals regional variations in the micromechanical properties of the pericellular and extracellular matrices of the meniscus, J Orthop Res, 31, 1218, 10.1002/jor.22362 Shu, 2019, Elevated hypertrophy, growth plate maturation, glycosaminoglycan deposition, and exostosis formation in the Hspg2 exon 3 null mouse intervertebral disc, Biochem J, 476, 225, 10.1042/BCJ20180695 Cohen, 1993, Structural characterization of the complete human perlecan gene and its promoter, Proc Natl Acad Sci USA, 90, 10404, 10.1073/pnas.90.21.10404 Arikawa-Hirasawa, 2002, Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia, Am J Hum Genet, 70, 1368, 10.1086/340390 Smith, 2010, Comparative immunolocalisation of perlecan with collagen II and aggrecan in human foetal, newborn and adult ovine joint tissues demonstrates perlecan as an early developmental chondrogenic marker, Histochem Cell Biol, 134, 251, 10.1007/s00418-010-0730-x Timpl, 1983, Nidogen: a new, self-aggregating basement membrane protein, FEBS J, 137, 455 Kohfeldt, 1998, Nidogen-2: a new basement membrane protein with diverse binding properties, J Mol Biol, 282, 99, 10.1006/jmbi.1998.2004 Salmivirta, 2002, Binding of mouse nidogen-2 to basement membrane components and cells and its expression in embryonic and adult tissues suggest complementary functions of the two nidogens, Exp Cell Res, 279, 188, 10.1006/excr.2002.5611 Aumailley, 1993, Nidogen mediates the formation of ternary complexes of basement membrane components, Kidney Int, 43, 7, 10.1038/ki.1993.3 Fox, 1991, Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV, EMBO J, 10, 3137, 10.1002/j.1460-2075.1991.tb04875.x Pöschl, 1996, Site-directed mutagenesis and structural interpretation of the nidogen binding site of the laminin gamma1 chain, EMBO J, 15, 5154, 10.1002/j.1460-2075.1996.tb00899.x Ries, 2001, Recombinant domains of mouse nidogen-1 and their binding to basement membrane proteins and monoclonal antibodies, Eur J Biochem, 268, 5119, 10.1046/j.0014-2956.2001.02437.x Dziadek, 1995, Role of laminin-nidogen complexes in basement membrane formation during embryonic development, Experientia, 51, 901, 10.1007/BF01921740 Balzano, 2019, Nidogen-1 contributes to the interaction network involved in pro-B cell retention in the peri-sinusoidal hematopoietic stem cell niche, Cell Rep, 26, 3257, 10.1016/j.celrep.2019.02.065 LeBleu, 2007, Structure and function of basement membranes, Exp Biol Med, 232, 1121, 10.3181/0703-MR-72 Böse, 2006, Loss of nidogen-1 and -2 results in syndactyly and changes in limb development, J Biol Chem, 281, 39620, 10.1074/jbc.M607886200 Murshed, 2000, The absence of nidogen 1 does not affect murine basement membrane formation, Mol Cell Biol, 20, 7007, 10.1128/MCB.20.18.7007-7012.2000 Schymeinsky, 2002, Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice, Mol Cell Biol, 22, 6820, 10.1128/MCB.22.19.6820-6830.2002 Bader, 2005, Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice, Mol Cell Biol, 25, 6846, 10.1128/MCB.25.15.6846-6856.2005 Köhling, 2006, Nidogen and nidogen-associated basement membrane proteins and neuronal plasticity, Neurodegener Dis, 3, 56, 10.1159/000092094 Carlin, 1981, Entactin, a novel basal lamina-associated sulfated glycoprotein, J Biol Chem, 256, 5209, 10.1016/S0021-9258(19)69388-9 Kimura, 1998, Entactin-2: a new member of basement membrane protein with high homology to entactin/nidogen, Exp Cell Res, 241, 36, 10.1006/excr.1998.4016 Hutter, 2000, Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes, Science, 287, 989, 10.1126/science.287.5455.989 Kang, 2000, Nidogen is nonessential and not required for normal type IV collagen localization in Caenorhabditis elegans, Mol Biol Cell, 11, 3911, 10.1091/mbc.11.11.3911 Kim, 2000, Positioning of longitudinal nerves in C. elegans by nidogen, Science, 288, 150, 10.1126/science.288.5463.150 Ackley, 2003, The basement membrane components nidogen and type XVIII collagen regulate organization of neuromuscular junctions in Caenorhabditis elegans, J Neurosci, 23, 3577, 10.1523/JNEUROSCI.23-09-03577.2003 Dziadek, 1985, Expression of nidogen and laminin in basement membranes during mouse embryogenesis and in teratocarcinoma cells, Dev Biol, 111, 372, 10.1016/0012-1606(85)90491-9 Miosge, 2000, Ultrastructural colocalization of nidogen-1 and nidogen-2 with laminin-1 in murine kidney basement membranes, Histochem Cell Biol, 113, 115, 10.1007/s004180050014 Miosge, 2000, Nidogen-1. Expression and ultrastructural localization during the onset of mesoderm formation in the early mouse embryo, J Histochem Cytochem, 48, 229, 10.1177/002215540004800208 Ekblom, 1994, Role of mesenchymal nidogen for epithelial morphogenesis in vitro, Development, 120, 2003, 10.1242/dev.120.7.2003 Kadoya, 1997, Importance of nidogen binding to laminin gamma1 for branching epithelial morphogenesis of the submandibular gland, Development, 124, 683, 10.1242/dev.124.3.683 Miosge, 2001, Nidogen-1 and nidogen-2 are found in basement membranes during human embryonic development, Histochem J, 33, 523, 10.1023/A:1014995523521 Kuri-Harcuch, 1984, Extracellular matrix production by mouse 3T3-F442A cells during adipose differentiation in culture, Differentiation, 28, 173, 10.1111/j.1432-0436.1984.tb00280.x Napolitano, 1963, Cytolysomes in metabolically active cells, J Cell Biol, 18, 478, 10.1083/jcb.18.2.478 Alvarez-Llamas, 2007, Characterization of the human visceral adipose tissue secretome, Mol Cell Proteomics, 6, 589, 10.1074/mcp.M600265-MCP200 Aratani, 1988, Enhanced synthesis and secretion of type IV collagen and entactin during adipose conversion of 3T3-L1 cells and production of unorthodox laminin complex, J Biol Chem, 263, 16163, 10.1016/S0021-9258(18)37573-2 Hackl, 2005, Molecular processes during fat cell development revealed by gene expression profiling and functional annotation, Genome Biol, 6, R108, 10.1186/gb-2005-6-13-r108 Kratchmarova, 2002, A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes, Mol Cell Proteomics, 1, 213, 10.1074/mcp.M200006-MCP200 Molina, 2009, Temporal profiling of the adipocyte proteome during differentiation using a five-plex SILAC based strategy, J Proteome Res, 8, 48, 10.1021/pr800650r Noro, 2013, Laminin production and basement membrane deposition by mesenchymal stem cells upon adipogenic differentiation, J Histochem Cytochem, 61, 719, 10.1369/0022155413502055 Ojima, 2016, Dynamics of protein secretion during adipocyte differentiation, FEBS open bio, 6, 816, 10.1002/2211-5463.12091 Patlaka, 2014, The growth factor-like adipokine tartrate-resistant acid phosphatase 5a interacts with the rod G3 domain of adipocyte-produced nidogen-2, Biochem Biophys Res Commun, 454, 446, 10.1016/j.bbrc.2014.10.112 Roca-Rivada, 2015, CILAIR-based secretome analysis of obese visceral and subcutaneous adipose tissues reveals distinctive ECM remodeling and inflammation mediators, Sci Rep, 5, 12214, 10.1038/srep12214 Sillat, 2012, Basement membrane collagen type IV expression by human mesenchymal stem cells during adipogenic differentiation, J Cell Mol Med, 16, 1485, 10.1111/j.1582-4934.2011.01442.x Vaicik, 2014, Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain, PLoS One, 9, 10.1371/journal.pone.0109854 Ono, 1990, Ascorbic acid phosphate stimulates type IV collagen synthesis and accelerates adipose conversion of 3T3-L1 cells, Exp Cell Res, 187, 309, 10.1016/0014-4827(90)90096-S Sephel, 1996, Expression of capillary basement membrane components during sequential phases of wound angiogenesis, Matrix Biol, 15, 263, 10.1016/S0945-053X(96)90117-1 Baluk, 2003, Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors, Am J Pathol, 163, 1801, 10.1016/S0002-9440(10)63540-7 Jiang, 2004, Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis, J Histochem Cytochem, 52, 1575, 10.1369/jhc.4A6353.2004 Niquet, 1996, Entactin immunoreactivity in immature and adult rat brain, Brain Res Dev Brain Res, 95, 227, 10.1016/0165-3806(96)00089-2 Ae Seo, 2007, Acute changes of nidogen immunoreactivity in the basal lamina of the spinal cord vessels following dorsal hemisection without correlative changes of nidogen gene expression, Acta histochemical, 109, 446, 10.1016/j.acthis.2007.04.004 Nicosia, 1994, Modulation of angiogenesis in vitro by laminin-entactin complex, Dev Biol, 164, 197, 10.1006/dbio.1994.1191 Titz, 2004, Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1, Cell Mol Life Sci, 61, 1826, 10.1007/s00018-004-4105-0 Mokkapati, 2008, Basement membranes in skin are differently affected by lack of nidogen 1 and 2, J Invest Dermatol, 128, 2259, 10.1038/jid.2008.65 Mokkapati, 2012, Absence of the basement membrane component nidogen 2, but not of nidogen 1, results in increased lung metastasis in mice, J Histochem Cytochem, 60, 280, 10.1369/0022155412436586 Semkova, 2014, Anti-angiogenic effect of the basement membrane protein nidogen-1 in a mouse model of choroidal neovascularization, Exp Eye Res, 118, 80, 10.1016/j.exer.2013.11.006 Marchand, 2019, Extracellular matrix scaffolding in angiogenesis and capillary homeostasis, Semin Cell Dev Biol, 89, 147, 10.1016/j.semcdb.2018.08.007 Thomas, 1993, Genes coding for basement membrane glycoproteins laminin, nidogen, and collagen IV are differentially expressed in the nervous system and by epithelial, endothelial, and mesenchymal cells of the mouse embryo, Exp Cell Res, 208, 54, 10.1006/excr.1993.1222 Kvist, 2008, The major basement membrane components localize to the chondrocyte pericellular matrix--a cartilage basement membrane equivalent?, Matrix Biol, 27, 22, 10.1016/j.matbio.2007.07.007 Kruegel, 2008, Nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis cartilage, Arthritis Rheum, 58, 1422, 10.1002/art.23480 Schminke, 2014, A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint, Cell Mol Life Sci, 71, 1081, 10.1007/s00018-013-1436-8 Miosge, 2002, Evidence of nidogen-2 compensation for nidogen-1 deficiency in transgenic mice, Matrix Biol, 21, 611, 10.1016/S0945-053X(02)00070-7 Schminke, 2016, Laminins and nidogens in the pericellular matrix of chondrocytes: their role in osteoarthritis and chondrogenic differentiation, Am J Pathol, 186, 410, 10.1016/j.ajpath.2015.10.014 Robson, 2016, Tissue-specific gene repositioning by muscle nuclear membrane proteins enhances repression of critical developmental genes during myogenesis, Mol Cell, 62, 834, 10.1016/j.molcel.2016.04.035 Fox, 2008, A synaptic nidogen: developmental regulation and role of nidogen-2 at the neuromuscular junction, Neural Dev, 3, 24, 10.1186/1749-8104-3-24 Godfrey, 1998, Basal lamina molecules are concentrated in myogenic regions of the mouse limb bud, Anat Embryol, 198, 481, 10.1007/s004290050198 Holland, 2013, Proteomic profiling of cardiomyopathic tissue from the aged mdx model of Duchenne muscular dystrophy reveals a drastic decrease in laminin, nidogen and annexin, Proteomics, 13, 2312, 10.1002/pmic.201200578 Neu, 2006, Differential expression of entactin-1/nidogen-1 and entactin-2/nidogen-2 in myogenic differentiation, Differentiation, 74, 573, 10.1111/j.1432-0436.2006.00100.x Langen, 2003, Enhanced myogenic differentiation by extracellular matrix is regulated at the early stages of myogenesis, In Vitro Cell Dev Biol Anim, 39, 163, 10.1007/s11626-003-0011-2 Funanage, 1992, Entactin promotes adhesion and long-term maintenance of cultured regenerated skeletal myotubes, J Cell Physiol, 150, 251, 10.1002/jcp.1041500205 Grefte, 2016, Impaired primary mouse myotube formation on crosslinked type I collagen films is enhanced by laminin and entactin, Acta Biomater, 30, 265, 10.1016/j.actbio.2015.11.009 He, 2018, Methyl-CpG-binding protein 2 mediates antifibrotic effects in scleroderma fibroblasts, Ann Rheum Dis, 77, 1208 Dubovy, 2006, A heterogeneous immunofluorescence staining for laminin-1 and related basal lamina molecules in the dorsal root ganglia following constriction nerve injury, Histochem Cell Biol, 125, 671, 10.1007/s00418-005-0115-8 Bryan, 2012, Spatiotemporal expression profiling of proteins in rat sciatic nerve regeneration using reverse phase protein arrays, Proteome Sci, 10, 1, 10.1186/1477-5956-10-9 Lee, 2007, Nidogen is a prosurvival and promigratory factor for adult Schwann cells, J Neurochem, 102, 686, 10.1111/j.1471-4159.2007.04580.x Lee, 2009, Nidogen plays a role in the regenerative axon growth of adult sensory neurons through Schwann cells, J Kor Med Sci, 24, 654, 10.3346/jkms.2009.24.4.654 Wolfstetter, 2019, Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning, Development, 146, dev168948 Vasudevan, 2010, Basement membrane protein nidogen-1 shapes hippocampal synaptic plasticity and excitability, Hippocampus, 20, 608 Moore, 2006, Stem cells and their niches, Science, 311, 1880, 10.1126/science.1110542 Gattazzo, 2014, Extracellular matrix: a dynamic microenvironment for stem cell niche, Biochim Biophys Acta, 1840, 2506, 10.1016/j.bbagen.2014.01.010 Rayagiri, 2018, Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal, Nat Commun, 9, 1075, 10.1038/s41467-018-03425-3 Sanes, 2003, The basement membrane/basal lamina of skeletal muscle, J Biol Chem, 278, 12601, 10.1074/jbc.R200027200 Barros, 2011, Extracellular matrix: functions in the nervous system, Cold Spring Harb Perspect Biol, 3, 10.1101/cshperspect.a005108 McMillan, 2003, Epidermal basement membrane zone components: ultrastructural distribution and molecular interactions, J Dermatol Sci, 31, 169, 10.1016/S0923-1811(03)00045-8 Daley, 2008, Extracellular matrix dynamics in development and regenerative medicine, J Cell Sci, 121, 255, 10.1242/jcs.006064 Spradling, 2001, Stem cells find their niche, Nature, 414, 98, 10.1038/35102160 Thomas, 2007, Chondrocyte death by apoptosis is associated with cartilage matrix degradation, Osteoarthritis Cartilage, 15, 27, 10.1016/j.joca.2006.06.012 Yurchenco, 1984, Self-assembly of basement membrane collagen, Biochemistry, 23, 1839, 10.1021/bi00303a040 Yurchenco, 1990, Heparin modulation of laminin polymerization, J Biol Chem, 265, 3981, 10.1016/S0021-9258(19)39691-7 Wang, 2009, Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus, Nat Rev Mol Cell Biol, 10, 75, 10.1038/nrm2594 Engler, 2006, Matrix elasticity directs stem cell lineage specification, Cell, 126, 677, 10.1016/j.cell.2006.06.044 Guilak, 2009, Control of stem cell fate by physical interactions with the extracellular matrix, Cell Stem Cell, 5, 17, 10.1016/j.stem.2009.06.016 McBeath, 2004, Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment, Dev Cell, 6, 483, 10.1016/S1534-5807(04)00075-9 Martino, 2010, The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain, Faseb J, 24, 4711 Iozzo, 2005, Basement membrane proteoglycans: from cellar to ceiling, Nat Rev Mol Cell Biol, 6, 646, 10.1038/nrm1702 Whitelock, 2008, Diverse cell signaling events modulated by perlecan, Biochemistry, 47, 11174, 10.1021/bi8013938 Hynes, 2009, The extracellular matrix: not just pretty fibrils, Science, 326, 1216, 10.1126/science.1176009 Walker, 2018, Role of extracellular matrix in development and cancer progression, Int J Mol Sci, 19, 3028, 10.3390/ijms19103028 Rozario, 2010, The extracellular matrix in development and morphogenesis: a dynamic view, Dev Biol, 341, 126, 10.1016/j.ydbio.2009.10.026 Theocharis, 2014, Cell–matrix interactions: focus on proteoglycan–proteinase interplay and pharmacological targeting in cancer, FEBS J, 281, 5023, 10.1111/febs.12927 Ho, 2008, Nidogens-Extracellular matrix linker molecules, Microsc Res Tech, 71, 387, 10.1002/jemt.20567 Chermnykh, 2018, Extracellular matrix as a regulator of epidermal stem cell fate, Int J Mol Sci, 19, 1003, 10.3390/ijms19041003 Kleinman, 1987, Role of basement membranes in cell differentiation, Ann N Y Acad Sci, 513, 134, 10.1111/j.1749-6632.1987.tb25004.x Dong, 2002, Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1, Lab Invest, 82, 1617, 10.1097/01.LAB.0000042240.52093.0F Higuchi, 2010, Synthesized basement membranes direct the differentiation of mouse embryonic stem cells into pancreatic lineages, J Cell Sci, 123, 2733, 10.1242/jcs.066886 Rodin, 2010, Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511, Nat Biotechnol, 28, 611, 10.1038/nbt.1620 Sun, 2017, The role of laminins in cartilaginous tissues: from development to regeneration, Eur Cell Mater, 34, 40, 10.22203/eCM.v034a03 Von der Mark, 2010, Nanoscale engineering of biomimetic surfaces: cues from the extracellular matrix, Cell Tissue Res, 339, 131, 10.1007/s00441-009-0896-5 Wang, 2019, Impact of fibronectin knockout on proliferation and differentiation of human infrapatellar fat pad-derived stem cells, Front Bioeng Biotechnol, 7, 321, 10.3389/fbioe.2019.00321 Taylor, 2011, Tendon is covered by a basement membrane epithelium that is required for cell retention and the prevention of adhesion formation, PLoS One, 6, 10.1371/journal.pone.0016337 Nishida, 2007, Transcriptome database KK-Periome for periodontal ligament development: expression profiles of the extracellular matrix genes, Gene, 404, 70, 10.1016/j.gene.2007.09.009 Kalluri, 2009, The basics of epithelial-mesenchymal transition, J Clin Invest, 119, 1420, 10.1172/JCI39104 Mohammadinejad, 2020, EMT signaling: potential contribution of CRISPR/Cas gene editing, Cell Mol Life Sci, 77, 2701, 10.1007/s00018-020-03449-3 Pastor-Pareja, 2020, Atypical basement membranes and basement membrane diversity - what is normal anyway?, J Cell Sci, 133, jcs241794, 10.1242/jcs.241794 Bechtel, 2012, Different domains in nidogen-1 and nidogen-2 drive basement membrane formation in skin organotypic cocultures, Faseb J, 26, 3637, 10.1096/fj.11-194597 Li, 2008, Activated Notch1 maintains the phenotype of radial glial cells and promotes their adhesion to laminin by upregulating nidogen, Glia, 56, 646, 10.1002/glia.20643 Thyboll, 2002, Deletion of the laminin α4 chain leads to impaired microvessel maturation, Mol Cell Biol, 22, 1194, 10.1128/MCB.22.4.1194-1202.2002 Jones, 2005, Laminin-6 assembles into multimolecular fibrillar complexes with perlecan and participates in mechanical-signal transduction via a dystroglycan-dependent, integrin-independent mechanism, J Cell Sci, 118, 2557, 10.1242/jcs.02395 Berk, 2007, ECM remodeling in hypertensive heart disease, J Clin Invest, 117, 568, 10.1172/JCI31044 Spence, 2004, Dystroglycan, a scaffold for the ERK-MAP kinase cascade, EMBO Rep, 5, 484, 10.1038/sj.embor.7400140 Lord, 2014, The role of vascular-derived perlecan in modulating cell adhesion, proliferation and growth factor signaling, Matrix Biol, 35, 112, 10.1016/j.matbio.2014.01.016