title: Down-regulation of tissue inhibitor of matrix metalloprotease-1 (TIMP-1) in aged human skin contributes to matrix degradation and impaired cell growth and survival.
abstract: Up regulation of matrix metalloproteinases (MMPs), particularly collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and gelatinase A (MMP-2) is responsible for the lysis of dermal collagen and elastin fibers during chronological skin aging. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is one representative of the natural MMP inhibitor family, encompassing four members. Its expression is decreased with fibroblast senescence, both ex vivo and in vivo, thus contributing to increased catabolic activity within dermis. TIMP-1 displays multiple biological functions. It inhibits most MMPs, except membrane-type MMP subfamily, with Ki in the subnanomolar range, but also interacts with the hemopexin-like (PEX) domain of pro MMP-9. Besides, it exhibits keratinocyte and fibroblast growth factor-like activity and has been described as a cell survival factor.
authors: Laboratoire de Biochimie, faculté de médecine, IFR53 Biomolécules, Centre National de la Recherche Scientifique (CNRS FRE 2534), Universite de Reims-Champagne Ardenne, 51, rue Cognacq-Jay, 51095 Reims, France. william.hornebeck@univ-reims.fr
authors: William
authors: W
authors: Hornebeck
mesh_terms: D000368:Aged; D002455:Cell Division; D002470:Cell Survival; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D012867:Skin / Q000166:cytology* / Q000473:pathology; D015595:Skin Aging / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1