title: Smooth muscle α actin (Acta2) and myofibroblast function during hepatic wound healing.
abstract: Smooth muscle α actin (Acta2) expression is largely restricted to smooth muscle cells, pericytes and specialized fibroblasts, known as myofibroblasts. Liver injury, associated with cirrhosis, induces transformation of resident hepatic stellate cells into liver specific myofibroblasts, also known as activated cells. Here, we have used in vitro and in vivo wound healing models to explore the functional role of Acta2 in this transformation. Acta2 was abundant in activated cells isolated from injured livers but was undetectable in quiescent cells isolated from normal livers. Both cellular motility and contraction were dramatically increased in injured liver cells, paralleled by an increase in Acta2 expression, when compared with quiescent cells. Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction. Additionally, Acta2 knockdown was associated with a significant reduction in Erk1/2 phosphorylation compared to control cells. The data indicate that Acta2 is important specifically in myofibroblast cell motility and contraction and raise the possibility that the Acta2 cytoskeleton, beyond its structural importance in the cell, could be important in regulating signaling processes during wound healing in vivo.
authors.affiliation: Department of Internal Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Don C
authors.initials: DC
authors.lastname: Rockey
authors.forename: Nate
authors.initials: N
authors.lastname: Weymouth
authors.forename: Zengdun
authors.initials: Z
authors.lastname: Shi
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014945:Wound Healing / Q000235:genetics*
chemical_list: D000199:Actins; D002251:Carbon Tetrachloride; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D034741:RNA, Small Interfering; C498862:Acta2 protein, rat