title: Whole animal knockout of smooth muscle alpha-actin does not alter excisional wound healing or the fibroblast-to-myofibroblast transition.
abstract: The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in wound closure. It has been hypothesized that smooth muscle α-actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle α-actin-null mice to test this hypothesis. Full-thickness excisional wounds closed at a similar rate in smooth muscle α-actin-null and wild-type mice. In addition, fibroblasts in smooth muscle α-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, showing that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α-actin-null and wild-type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-β1. Smooth muscle γ-actin and skeletal muscle α-actin were expressed in smooth muscle α-actin-null myofibroblasts, as shown by immunostaining, real-time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle α-actin is not necessary for myofibroblast formation and function and for wound closure, and that smooth muscle γ-actin and skeletal muscle α-actin may be able to functionally compensate for the lack of smooth muscle α-actin in myofibroblasts.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. james-tomasek@ouhsc.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Tomasek
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Haaksma
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: Eric W
authors.initials: EW
authors.lastname: Howard
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000473:pathology*; D022001:Focal Adhesions / Q000473:pathology*; D006097:Granulation Tissue / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing; D014947:Wounds and Injuries / Q000473:pathology*
chemical_list: D000199:Actins; C544013:alpha-smooth muscle actin, mouse