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Originally published online as doi:10.2353/ajpath.2009.080779 on April 6, 2009

Published online before print April 6, 2009
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(American Journal of Pathology. 2009;174:1847-1856.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080779

Rac1 Expression by Fibroblasts Is Required for Tissue Repair in Vivo

Shangxi Liu, Mohit Kapoor and Andrew Leask

From the Canadian Institute of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and the Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada

Tissue repair requires that fibroblasts migrate into the wound to produce and remodel extracellular matrix, a process that requires adhesion. Failure to suppress the tissue repair program results in fibrotic disorders that are characterized by excessive adhesive signaling. The role of specific components of adhesive signaling in fibrogenic responses is unclear, but may involve small GTPases such as Rac1. To address the functions of Rac1 in fibroblasts, we generated mice containing a fibroblast-specific deletion of Rac1. These mice show delayed cutaneous wound closure, including reduced collagen production and myofibroblast formation. In cultured Rac1-deficient fibroblasts, adhesion, spreading, and migration were significantly inhibited. Rac1-deficient fibroblasts possessed impaired myofibroblast formation and function as visualized by reduced {alpha}-smooth muscle actin expression as well as matrix contraction. Both in vivo and in vitro, Rac1- deficient fibroblasts showed a reduced generation of reactive oxygen species; in vitro, hydrogen peroxide alleviated the phenotype of Rac1-deficient fibroblasts. Thus, Rac1 is an essential signaling integrator that is required for normal wound healing and dermal homeostasis.






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Copyright © 2009 by the American Society for Investigative Pathology.