Multiple roles of alpha-smooth muscle actin in mechanotransduction.
Alpha-smooth muscle actin (SMA), an actin isoform that contributes to cell-generated mechanical tension, is normally restricted to cells of vascular smooth muscle, but SMA can also be expressed in certain non-muscle cells, most notably myofibroblasts. These cells are present in healing wounds, scars, and fibrocontractive lesions where they contribute to fibrosis. In myofibroblasts, cell-generated traction forces associated with SMA contribute to matrix remodeling, but exogenous mechanical forces can also increase SMA expression. Force-induced SMA utilizes a feed-forward amplification loop involving a priori SMA in focal adhesions, the binding of the p38 MAP kinase to SMA filaments, activation of Rho and binding of serum response factor to the CArG-B box of the SMA promoter. Thus, in addition to its importance as a structural protein in tissue remodeling and contraction, SMA may serve as a mechanotransducer, based on its ability to physically link mechanosensory elements and to enhance its own, force-induced expression.
Wang
Jiaxu
J
CIHR Group in Matrix Dynamics Faculty of Dentistry, Room 244, Fitzgerald Building, University of Toronto, 150 College Street, Toronto, Ontario, Canada M5S 3E2.
Zohar
Ron
R
McCulloch
Christopher A
CA
D000199:Actins / Q000502:physiology*; D000818:Animals; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D026362:Serum Response Factor / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D026362:Serum Response Factor; D048051:p38 Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins