title: Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms.
abstract: Thrombospondin 1 (TSP1) plays major roles in both physiologic and pathologic tissue repair. TSP1 through its type 1 repeats is a known regulator of latent TGF-β activation and plays a role in wound healing and fibrosis. Binding of the TSP N-terminal domain to cell surface calreticulin in complex with LDL-receptor related protein 1 stimulates intermediate cell adhesion, cell migration, anoikis resistance, collagen expression and matrix deposition in an in vivo model of the foreign body response. There is also emerging evidence that TSP EGF-like repeats alter endothelial cell-cell interactions and stimulate epithelial migration through transactivation of EGF receptors. The mechanisms underlying these functions of TSP1 and the implications for physiologic and pathologic wound repair and fibrosis will be discussed.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, United States.
authors.forename: Mariya T
authors.initials: MT
authors.lastname: Sweetwyne
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Murphy-Ullrich
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000737:chemistry*; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D066246:ErbB Receptors / Q000737:chemistry / Q000502:physiology; D005355:Fibrosis / Q000503:physiopathology*; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000737:chemistry / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000737:chemistry*; D014945:Wound Healing
chemical_list: D037282:Calreticulin; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D066246:ErbB Receptors