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JCS ePress online publication date 8 Apr 2008
doi: 10.1242/jcs.021683

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Research Article

Fibroblast migration is mediated by CD44-dependent TGF{beta} activation


Pinak S. Acharya, Sonali Majumdar, Michele Jacob, James Hayden, Paul Mrass, Wolfgang Weninger, Richard K. Assoian, and Ellen Puré*
* Author for correspondence (e-mail: pure{at}wistar.org)

CD44 contributes to inflammation and fibrosis in response to injury. As fibroblast recruitment is critical to wound healing, we compared cytoskeletal architecture and migration of wild-type (CD44WT) and CD44-deficient (CD44KO) fibroblasts. CD44KO fibroblasts exhibited fewer stress fibers and focal adhesion complexes, and their migration was characterized by increased velocity but loss of directionality, compared with CD44WT fibroblasts. Mechanistically, we demonstrate that CD44WT cells generated more active TGF{beta} than CD44KO cells and that CD44 promotes the activation of TGF{beta} via an MMP-dependent mechanism. Reconstitution of CD44 expression completely rescued the phenotype of CD44KO cells whereas exposure of CD44KO cells to exogenous active TGF{beta} rescued the defect in stress fibers and migrational velocity, but was not sufficient to restore directionality of migration. These results resolve the TGF{beta}-mediated and TGF{beta}-independent effects of CD44 on fibroblast migration and suggest that CD44 may be critical for the recruitment of fibroblasts to sites of injury and the function of fibroblasts in tissue remodeling and fibrosis.






© The Company of Biologists Ltd 2008