title: Genetic aberrations in tissue inhibitor of metalloproteinases-3 lead to manifestations of the myofibroblast phenotype in mouse fibroblasts and fibroblasts of patients with Sorsby fundus dystrophy.
abstract: Mutations in the C-terminal domain of tissue inhibitor of metalloproteinases-3 (TIMP-3) lead to autosomal dominant hereditary disease of the retina (Sorsby fundus dystrophy). Mouse knock-out and heterozygous knock-in fibroblasts and fibroblasts from patients with Sorsby fundus dystrophy exhibit some characteristics of myofibroblasts. Genetic changes in the timp-3 gene (TIMP-3) lead to a shift towards the myofibroblast phenotype in the fibroblast culture. It is hypothesized that Timp-3 (TIMP-3) plays a role of antitransformation agent preventing myofibroblast transformation in vivo and that the pathogenesis of Sorsby fundus dystrophy is associated with the loss of the antitransformation function by the mutant protein.
authors.affiliation: Research Center of Obstetrics, Gynecology, and Perinatology, Russian Academy of Medical Sciences. soboleva_galina@hotmail.com
authors.forename: G M
authors.initials: GM
authors.lastname: Soboleva
authors.forename: G T
authors.initials: GT
authors.lastname: Sukhikh
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D012164:Retinal Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000199:Actins; D019717:Tissue Inhibitor of Metalloproteinase-3