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Selective reduction of fibrotic markers in repairing corneas of mice deficient in Smad3
Author(s) -
Stramer Brian M.,
Austin Jeffrey S.,
Roberts Anita B.,
Elizabeth Fini M.
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20215
Subject(s) - fibronectin , fibrosis , transforming growth factor beta , stromal cell , corneal epithelium , inflammation , myofibroblast , wound healing , transforming growth factor , cornea , pathology , biology , cytokine , epithelium , microbiology and biotechnology , cancer research , immunology , medicine , extracellular matrix , neuroscience
The cytokine transforming growth factor‐β (TGF‐β) is a key mediator of fibrosis in all organs. Expression of fibrotic markers in repairing cutaneous wounds is reduced in mice lacking Smad3, a downstream cytoplasmic mediator of TGF‐β signaling (Ashcroft et al., 1999, Nat Cell Biol 1(5):260–266). This is correlated with a reduction in inflammation, and thus in the blood elements thought to be a significant source of TGF‐β at the wound site, the principle form being TGF‐β1. Since the major cellular source of TGF‐β in corneal wounds is the epithelium, and the principal isoform is TGF‐β2, we investigated whether Smad3 deficiency has similar anti‐fibrotic effects on corneal repair. In contrast to the situation of cutaneous repair, expression of the fibrotic marker, fibronectin, was equivalent in corneal repair tissue of Smad3−/− mice as compared to their +/− littermates, even though expression of a second fibrotic marker not previously examined in cutaneous wounds, α‐smooth muscle (sm) actin, was reduced. Also unlike in cutaneous wounds, the inflammatory response was unaffected. These differences between corneal and cutaneous repair correlated with the lack of apparent change in the levels of corneal TGF‐β2. There was a significant reduction of α‐sm actin expression in stromal cell cultures established from Smad3−/− mice as compared to their +/− littermates, but the rate of cell proliferation stimulated by TGF‐β, as well as expression of fibronectin, was unaffected. Therefore, a deficiency in Smad3 has different effects on corneal and cutaneous repair, probably due to the difference in cellular source and principal isoform of the TGF‐β involved. © 2004 Wiley‐Liss, Inc.