Whole animal knockout of smooth muscle alpha-actin does not alter excisional wound healing or the fibroblast-to-myofibroblast transition

• Published in: Wound repair and regeneration 2013-01, Vol.21 (1), p.166-176
• Main Authors: Tomasek, James J., Haaksma, Carol J., Schwartz, Robert J., Howard, Eric W.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Blotting, Western; Cell Differentiation; Cells, Cultured; Fibroblasts - pathology; Focal Adhesions - pathology; Granulation Tissue - pathology; Male; Mice; Mice, Inbred C57BL; Myofibroblasts - pathology; Real-Time Polymerase Chain Reaction; Wound Healing; Wounds and Injuries - pathology
• ISSN: 1067-1927; 1524-475X
• DOI: 10.1111/wrr.12001

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.