Main ECM molecules, some of their functional roles, and selected genetic and other diseases related to individual molecules
| Group | Distribution/Function | Genetic Disease(s) | Other disease(s) |
|---|---|---|---|
| Collagens | |||
| Fibrillar collagens | |||
| I | Structural component of all tissues except cartilage; e.g. bone, dermis (Gelse et al., 2003), vessel wall (Katsuda et al., 1992; Rauterberg et al., 1993), and heart (Marijianowski et al., 1994) | Osteogenesis imperfecta (Bonadio and Byers, 1985); classic type Ehlers-Danlos syndrome (Nuytinck et al., 2000) | Atherosclerosis (Katsuda et al., 1992; Rauterberg et al., 1993); hypertensive heart disease (López et al., 2001; Díez et al., 2005); fibrotic diseases including chronic kidney diseases (Alexakis et al., 2006) |
| II | Predominant component of cartilage (Bruckner and van der Rest, 1994); mediates interactions with proteoglycans (Mayne, 1989) | Stickler syndrome type I (Maumenee, 1979; Ahmad et al., 1991); spondyloepiphyseal dysplasia (Tiller et al., 1995); achondrogenesis (Eyre et al., 1986); Kniest dysplasia (Winterpacht et al., 1993) | Osteoarthritis (Nelson et al., 1998) |
| III | Dominant collagen type of granulation tissue, and also, e.g., muscles and artery wall (Katsuda et al., 1992; Linehan et al., 2001); produced by young fibroblasts before type I collagen (Voermans et al., 2008) | Vascular Ehlers-Danlos syndrome (Pope et al., 1975; Pepin et al., 2000) | Atherosclerosis (Katsuda et al., 1992); hypertensive heart disease (Díez et al., 2005); fibrotic diseases, e.g. chronic kidney diseases (Alexakis et al., 2006) |
| V | Structural component of basement membrane (Graham et al., 2008); interacts with type I collagen (Birk, 2001); inhibits endothelial cell adhesion, proliferation (Fukuda et al., 1988), and adhesion (Hashimoto et al., 1991) | Classic type Ehlers-Danlos syndrome (Nicholls et al., 1996; Richards et al., 1998) | Atherosclerosis (Katsuda et al., 1992); collagenofibrotic glomerulopathy (Morita et al., 2003); bronchiolitis obliterans syndrome (Burlingham et al., 2007) |
| XI | Structural component of articular cartilage (Mayne, 1989) and ear (Nerlich, 1995); modulates cartilage matrix homeostasis (Eyre, 2004) | Stickler syndrome type II (Richards et al., 1996) and type III (Brunner et al., 1994); Marshall syndrome (Majava et al., 2007b); otospondylomegaepiphyseal dysplasia (Melkoniemi et al., 2000) | Disc herniation (Mio et al., 2007) |
| Nonfibrillar collagens | |||
| IV | Structural component of basement membrane (LeBleu et al., 2007); e.g., in kidney (Smith et al., 1989); associated with angiogenesis (Xu et al., 2001) | Alport syndrome (Barker et al., 1990); hereditary angiopathy (Breedveld et al., 2006) | Diabetic nephropathy (Cohen et al., 2001); organ or tumor fibrosis (Kalluri, 2003); cancer progression (Tanjore and Kalluri, 2006) |
| VIII | Structural component of extracellular matrices, e.g. in sclera (Shuttleworth, 1997) and vasculature (Plenz et al., 2003); involved in stabilization of membranes, angiogenesis and interacts with ECM molecules (Sutmuller et al., 1997; Plenz et al., 2003) | Corneal endothelial dystrophy, e.g., Fuchs' endothelial dystrophy (Biswas et al., 2001) | Atherosclerosis (Plenz et al., 2003); tumor progression (Koon et al., 2004) |
| X | Structural component of hypertrophic cartilage (Gelse et al., 2003); regulates matrix mineralization and compartmentalization of ECM components (Shen, 2005) | Schmid-type metaphyseal chondroplasia (Warman et al., 1993) | Osteochondritis dissecans (Aurich et al., 2006) |
| Association collagens | |||
| VI | Dominant structural component of connective tissue; e.g., in vessels, liver (von der Mark et al., 1984), and muscle (Engvall et al., 1986) | Muscle disorders, e.g., myosclerosis myopathy (Merlini et al., 2008b) | Atherosclerosis (Katsuda et al., 1992) |
| VII | Structural component of basement membrane (Sakai et al., 1986); interacts with other ECM components (Keene et al., 1987) | Dystrophic epidermolysis bullosa (Hovnanian et al., 1992) | Epidermolysis bullosa acquisita (Chen et al., 2007) |
| IX | Structural component of cartilage (Olsen, 1997); interacts with collagen type II (Eyre, 2004) | Stickler syndrome (Van Camp et al., 2006); multiple epiphyseal dysplasia (Bönnemann et al., 2000); Scheuermann disease (Karppinen et al., 2003) | |
| XII | Structural component of connective tissue, e.g., in skin (Wälchli et al., 1994); interacts with other matrix components (Voermans et al., 2008) | Diabetic retinopathy (Ljubimov et al., 1996); keratoconus (Cheng et al., 2001) | |
| XIV | Structural component of connective tissue, e.g., in blood vessels (Castagnola et al., 1992); interacts with other ECM components (Ehnis et al., 1997) | Diabetic retinopathy (Ljubimov et al., 1996) | |
| XIX | Structural component of basement membrane (Myers et al., 1997); associated with muscle cells (Myers et al., 1999) | Rhabdomyosarcomas (Myers et al., 1999); breast cancer (Amenta et al., 2003) | |
| Transmembrane collagens | |||
| XIII | Structural component of, e.g., skin (Peltonen et al., 1999); interacts with other ECM components, e.g., proteoglycans (Michelacci, 2003) | Tumor development (Väisänen et al., 2005); thyroid-associated ophthalmopathy (Yamada et al., 2000) | |
| XVII | Structural component of cutaneous basement membrane (Uitto and Pulkkinen, 1996); involved in cell-matrix adhesion (Van den Bergh and Giudice, 2003) | Non-Herlitz junctional epidermolysis bullosa (Bauer and Lanschuetzer, 2003) | |
| Multiplexins | |||
| XV | Structural component of basement membrane (Myers et al., 1996); acts as structural organizer of ECM (Amenta et al., 2005) | Tumorigenesis (Amenta et al., 2003, Fukushige et al., 2005) | |
| XVIII | Structural component of basement membrane (Saarela et al., 1998); inhibition angiogenesis and tumor growth (Myllyharju and Kivirikko, 2001) | Knobloch syndrome (Suzuki et al., 2002) | Fibrotic diseases, e.g., liver fibrosis (Musso et al., 1998) |
| Elastin and microfibrillar proteins | |||
| Elastin | Structural component of elastic fibers (Rosenbloom et al., 1993); provides elasticity to different tissues, e.g., lungs, large blood vessels, and dermis (Ross, 1973) | Supravalvular aortic stenosis (Ewart et al., 1993); cutis laxa (Tassabehji et al., 1998); Williams-Beuren syndrome (Milewicz et al., 2000) | Hypertension (Martyn and Greenwald, 1997); pulmonary emphysema (Snider et al., 1991); arterial aneurysms (Alberto et al., 2008) |
| Fibrillin 1 | Major structural component of microfibrils together with fibrillin-2 (Ramirez and Pereira, 1999); involved in tissue homeostasis (Zhang et al., 1995) | Marfan's syndrome (Robinson and Booms, 2001); Shprintzen-Goldberg syndrome (Sood et al., 1996); Weill-Marchesani syndrome (Faivre et al., 2003) | Atherosclerosis (Seyama and Wachi, 2004); pulmonary emphysema (Robbesom et al., 2008) |
| Fibrillin 2 | Major structural component of microfibrils together with fibrillin-1 (Ramirez and Pereira, 1999) | Congenital contractural arachnodactyly (Beals and Hecht, 1971) | |
| Fibulin 1 | Structural component of basement membranes (Pan et al., 1993a); interacts with other ECM molecules, e.g., laminins (Timpl and Brown, 1994); modulates platelet adhesion (Godyna et al., 1996) | Synpolydactyly (Debeer et al., 2002); autosomal recessively inherited vitreoretinal dystrophy (Weigell-Weber et al., 2003) | Prostate cancer (Wlazlinski et al., 2007); gastric cancer (Cheng et al., 2008) |
| Fibulin 2 | Structural component of basement membranes (Pan et al., 1993b); involved in vasculogenesis and angiogenesis (Tsuda et al., 2001) | Breast cancer progression (Yi et al., 2007) | |
| Fibulin 3 | Structural component of blood vessels (Giltay et al., 1999) | Macular degenerative disease (Klenotic et al., 2004) | |
| Fibulin 4 | Structural component of blood vessels (Giltay et al., 1999) | Cutis laxa (Hucthagowder et al., 2006) | Colon tumorigenesis (Gallagher et al., 2001); prostate cancer (Wlazlinski et al., 2007) |
| Fibulin 5 | Organizer of elastic fibers (Yanagisawa et al., 2002); regulator of angiogenesis (Kowal et al., 1999); associated with suppression of tumorigenesis (Albig and Schiemann, 2005) | Cutis laxa (Loeys et al., 2002); age-related macular degeneration (Stone et al., 2004) | Prostate cancer (Wlazlinski et al., 2007) |
| Fibulin 6 | Organizer in cell-cell and cell-matrix interactions (Vogel and Hedgecock, 2001) | Macular degeneration (Schultz et al., 2003) | |
| Fibulin 7 | Cell adhesion molecule, associated with, e.g., dentin formation (de Vega et al., 2007) | ||
| Emilin 1 | Microfibril-associated protein (Mongiat et al., 2000); involved in vascular cell morphology and elastogenesis (Zanetti et al., 2004) | Hypertension (Raman and Cobb, 2006) | |
| Proteoglycans and glycosaminoglycans | |||
| Hyaluronan | Major structural carbohydrate component of the ECM (Chen and Abatangelo, 1999); involved in angiogenesis, cell motility, wound healing and cell adhesion (Stuhlmeier, 2006) | Tumorigenesis (Auvinen et al., 2000; Hiltunen et al., 2002; Toole, 2002; Heldin et al., 2008); atherosclerosis and restenosis (Wight, 2008); inflammatory bowel disease (de La Motte et al., 1999; de la Motte et al., 2003) | |
| Hyalectans | |||
| Aggrecan | Structural component of articular cartilage (Dudhia, 2005); interacts with hyaluronan (Kiani et al., 2002) | Intervertebral disc degeneration (Solovieva et al., 2007); spondyloepiphyseal dysplasia (Gleghorn et al., 2005) | Osteoarthritis (Fosang and Little, 2008) |
| Brevican | Abundant proteoglycan in adult brain (Yamaguchi, 1996) | Tumor progression (Hu et al., 2008) | |
| Neurocan | Structural component of the ECM of brain (Grumet et al., 1996); interacts with other ECM molecules and cell surface receptors (Rauch et al., 2001) | ||
| Versican | Structural component of the ECM, e.g., in blood vessels (Kenagy et al., 2006); mediates cell adhesion and migration (Ang et al., 1999) | Erosive vitreoretinopathy and Wagner disease (Mukhopadhyay et al., 2006) | Atherosclerosis and restenosis (Wight and Merrilees, 2004); tumorigenesis (Nara et al., 1997; Suwiwat et al., 2004) and metastasis (Kim et al., 2009) |
| Small leucine-rich proteoglycans (SLRPs) | |||
| Asporin | Structural component of articular cartilage (Lorenzo et al., 2001) | Osteoarthritis (Kizawa et al., 2005) | Bone and joint diseases (Ikegawa, 2008) |
| Biglycan | Structural component of, e.g., vascular wall (Williams, 2001); binds growth factors such as TGF-β and regulates its activity (Hildebrand et al., 1994) | Abdominal aortic aneurysms (Tamarina et al., 1998) | |
| Decorin | Structural component of, e.g., skin (Reed and Iozzo, 2002) and vascular wall (Williams, 2001); regulates collagen fibrillogenesis (Zhang et al., 2006); binds growth factors such as TGF-β and neutralizes its activity (Yamaguchi et al., 1990); involved in angiogenesis (Järveläinen et al., 1992 and 2006) | Congenital stromal dystrophy (Bredrup et al., 2005) | Tumorigenesis (Grant et al., 2002; Goldoni et al., 2008; Salomäki et al., 2008); osteoarthritis (Melrose et al., 2008); renal disease (Schaefer et al., 1998 and 2001) |
| Fibromodulin | Binds to specific collagen types (Hedbom and Heinegård, 1989) and regulates their fibril formation (Svensson et al., 1999); binds growth factors such as TGF-β and regulates its activity (Hildebrand et al., 1994) | Myopia (Majava et al., 2007a) | Osteoarthritis (Melrose et al., 2008) |
| Keratocan | Structural component of e.g. cornea (Kao and Liu, 2002) | Cornea plana (Pellegata et al., 2000) | Osteoarthritis (Melrose et al., 2008) |
| Lumican | Structural component of e.g. cornea (Kao and Liu, 2002) | Myopia (Wang et al., 2006; Majava et al., 2007a) | Fibrosis and tumor growth (Naito, 2005); atherosclerosis (Onda et al., 2002) |
| Osteoadherin | Promotes αv/β3-integrin mediated cell binding (Wendel et al., 1998); regulation of complement activation (Sjöberg et al., 2009) | ||
| PRELP | Anchors basement membranes to the underlying connective tissue (Bengtsson et al., 2002) | Myopia (Majava et al., 2007a) | |
| Epiphycan | Involved in chondrogenesis (Knudson and Knudson, 2001) | ||
| Opticin | Component of the vitreous humour of the eye (Reardon et al., 2000) and cartilage (Monfort et al., 2008) | Myopia (Majava et al., 2007a); primary open angle glaucoma (Acharya et al., 2007) | |
| Osteoglycin/Mimecan | Component of the vascular wall (Shanahan et al., 1997); regulation of collagen fibrillogenesis (Tasheva et al., 2002) | ||
| Chondroadherin | Component of the cornea, brain, and skeletal muscle, retina and lens (Tasheva et al., 2004); regulates chondrocyte growth and proliferation (Shen et al., 1998) | ||
| Nyctalopin | Essential for retinal synaptic transmission (Bahadori et al., 2006) | Congenital stationary night blindness (Bech-Hansen et al., 2000; Pusch et al., 2000) | |
| Tsukushi | Bone morphogenic protein antagonist (Ohta et al., 2004) | ||
| Podocan | Component of glomeruli (Ross et al., 2003) | Glomerulosclerosis (Ross et al., 2003) | |
| Podocan like protein 1 | Facilitates nephrin signaling (Huber et al., 2001) | ||
| Basement membrane proteoglycans | |||
| Agrin | Modulator of synaptogenesis (Bezakova and Ruegg, 2003; Williams et al., 2008) | Cirrhosis and hepatocellular carcinoma (Tátrai et al., 2006); Alzheimer's disease (Berzin et al., 2000) | |
| Bamacan | Structural component of basement membrane (Couchman et al., 1996) | Diabetic retinopathy (Ljubimov et al., 1996) | |
| Perlecan | Structural component of basement membrane (Iozzo, 1994); regulates, e.g., cell migration and proliferation (Whitelock et al., 2008); involved in angiogenesis (Bix and Iozzo, 2008) | Dyssegmental dysplasia (Silverman-Handmaker type) (Arikawa-Hirasawa et al., 2001); Schwartz-Jampel syndrome (Arikawa-Hirasawa et al., 2002) | Diabetic retinopathy (Ljubimov et al., 1996); tumor growth (Mathiak et al., 1997); Alzheimer's disease (Castillo et al., 1997) |
| Other extracellular proteoglycans | |||
| PG-100 | Proteoglycan form of colony-stimulating factor-1 (Partenheimer et al., 1995) | Hepatitis and liver fibrosis (Högemann et al., 1997) | |
| Testican-1, -2, and -3 | Inhibition of different proteases (Nakada et al., 2003; Edgell et al., 2004) | Testican-3: T-cell leukemia (Kamioka et al., 2009) | |
| Noncollagenous ECM glycoproteins | |||
| Fibronectins (>20 different isoforms) | Involved in cellular adhesion (Akiyama et al., 1981), fibril (Kadler et al., 2008) and ECM assembly (Couchman et al., 1990), tissue injury and inflammation (Satoi et al., 1999; Okamura et al., 2001); regulation of vascular morphogenesis including angiogenesis (Astrof and Hynes, 2009) | Glomerulopathy (Castelletti et al., 2008) | Idiopathic pulmonary fibrosis (Kuhn and McDonald, 1991); cancer (Korc, 2007; Astrof and Hynes, 2009); tendinopathy (Riley, 2007) |
| Laminins | Involved in cell adhesion, migration and differentiation (Colognato and Yurchenco, 2000; Patarroyo et al., 2002) | Congenital muscular dystrophy (Hall et al., 2007); epidermolysis bullosa (Uitto et al., 1994); Pierson syndrome (Zenker et al., 2004) | Tumor progression (Ziober et al., 1996; Ono et al., 1999, Rabinovitz et al., 2001; Nelson et al., 2008) |
| SPARC (secreted protein, acidic and rich in cysteine) | Inhibition of cell proliferation (Yan and Sage, 1999) and angiogenesis (Chlenski et al., 2006) | Tumor progression and metastasis (Porter et al., 1995; Watkins et al., 2005; Clark and Sage, 2008; Podhajcer et al., 2008); idiopathic osteoporosis (Delany et al., 2008) | |
| Tenascins (tenascin-C, -R, -X, and -W) | Involved in cell adhesion, migration and growth (Chiquet-Ehrismann and Chiquet, 2003), wound healing, and neovascularization (Hsia and Schwarzbauer, 2005; Trebaul et al., 2007) | Ehlers-Danlos syndrome (Burch et al., 1997; Mao and Bristow, 2001) | Fibrotic diseases, inflammation, tumorigenesis (Chiquet-Ehrismann and Chiquet, 2003) |
| Thrombospondins (1–5) | Involved in cell migration (Yabkowitz et al., 1993), platelet aggregation, inflammatory response, and wound healing (Adams and Lawler, 2004) | Thrombospondin-5; pseudoachondroplasia and multiple epiphyseal dysplasia (Posey et al., 2008) | Tumor progression (Lawler and Detmar, 2004; Kazerounian et al., 2008); atherosclerosis (Roth et al., 1998; Takahashi et al., 2008) |
| Nidogen/entactin (nidogen 1 and nidogen 2) | Involved in cell adhesion (Yi et al., 1998; Grimpe et al., 1999), wound healing (Sephel et al., 1996) and basement membrane stabilization (Ho et al., 2008) | Osteoarthritis (Kruegel et al., 2008); cancer and tumor progression (Oivula et al., 1999; Ulazzi et al., 2007; Douglas et al., 2008) |