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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 ?-actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle ?-actin-null mice to test this hypothesis. Full-thickness excisional wounds closed at a similar rate in smooth muscle ?-actin-null and wild-type mice. In addition, fibroblasts in smooth muscle ?-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 ?-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-?1. Smooth muscle ?-actin and skeletal muscle ?-actin were expressed in smooth muscle ?-actin-null myofibroblasts, as shown by immunostaining, real-time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle ?-actin is not necessary for myofibroblast formation and function and for wound closure, and that smooth muscle ?-actin and skeletal muscle ?-actin may be able to functionally compensate for the lack of smooth muscle ?-actin in myofibroblasts.

SUBMITTER: Tomasek JJ 

PROVIDER: S-EPMC3540133 | biostudies-literature | 2013 Jan-Feb

REPOSITORIES: biostudies-literature

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

Tomasek James J JJ   Haaksma Carol J CJ   Schwartz Robert J RJ   Howard Eric W EW  

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 20121218 1


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 i  ...[more]

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