title: Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts.
abstract: Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural and biochemical features of smooth muscle (SM) cells, including the presence of microfilament bundles and the expression of alpha-SM actin, the actin isoform typical of vascular SM cells. Myofibroblasts have been proposed to play a role in wound contraction and in retractile phenomena observed during fibrotic diseases. We show here that the subcutaneous administration of transforming growth factor-beta 1 (TGF beta 1) to rats results in the formation of a granulation tissue in which alpha-SM actin expressing myofibroblasts are particularly abundant. Other cytokines and growth factors, such as platelet-derived growth factor and tumor necrosis factor-alpha, despite their profibrotic activity, do not induce alpha-SM actin in myofibroblasts. In situ hybridization with an alpha-SM actin probe shows a high level of alpha-SM actin mRNA expression in myofibroblasts of TGF beta 1-induced granulation tissue. Moreover, TGF beta 1 induces alpha-SM actin protein and mRNA expression in growing and quiescent cultured fibroblasts and preincubation of culture medium containing whole blood serum with neutralizing antibodies to TGF beta 1 results in a decrease of alpha-SM actin expression by fibroblasts in replicative and non-replicative conditions. These results suggest that TGF beta 1 plays an important role in myofibroblast differentiation during wound healing and fibrocontractive diseases by regulating the expression of alpha-SM actin in these cells.
authors.affiliation: University of Geneva, Department of Pathology, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Desmoulière
authors.forename: A
authors.initials: A
authors.lastname: Geinoz
authors.forename: F
authors.initials: F
authors.lastname: Gabbiani
authors.forename: G
authors.initials: G
authors.lastname: Gabbiani
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha