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Akt‐mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation
Author(s) -
Paterno Josemaria,
Vial Ivan N.,
Wong Victor W.,
Rustad Kristine C.,
Sorkin Michael,
Shi Yubin,
Bhatt Kirit A.,
Thangarajah Hariharan,
Glotzbach Jason P.,
Gurtner Geoffrey C.
Publication year - 2010
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2010.00643.x
Subject(s) - mechanotransduction , hypertrophic scar , protein kinase b , pi3k/akt/mtor pathway , wortmannin , phosphorylation , microbiology and biotechnology , focal adhesion , fibroblast , fibrosis , in vivo , chemistry , signal transduction , cancer research , pathology , medicine , biology , in vitro , biochemistry
Although numerous factors are implicated in skin fibrosis, the exact pathophysiology of hypertrophic scarring remains unknown. We recently demonstrated that mechanical force initiates hypertrophic scar formation in a murine model, potentially enhancing cellular survival through Akt. Here, we specifically examined Akt‐mediated mechanotransduction in fibroblasts using both strain culture systems and our murine scar model. In vitro, static strain increased fibroblast motility, an effect blocked by wortmannin (a phosphoinositide‐3‐kinase/Akt inhibitor). We also demonstrated that high‐frequency cyclic strain was more effective at inducing Akt phosphorylation than low frequency or static strain. In vivo, Akt phosphorylation was induced by mechanical loading of dermal fibroblasts in both unwounded and wounded murine skin. Mechanically loaded scars also exhibited strong expression of α‐smooth muscle actin, a putative marker of pathologic scar formation. In vivo inhibition of Akt increased apoptosis but did not significantly abrogate hypertrophic scar development. These data suggest that although Akt signaling is activated in fibroblasts during mechanical loading of skin, this is not the critical pathway in hypertrophic scar formation. Future studies are needed to fully elucidate the critical mechanotransduction components and pathways which activate skin fibrosis.