Transforming growth factor-beta promotes fibroblast apoptosis induced by H2O2

Transforming growth factor-beta (TGF-beta) is believed to play a central role in fibroblastic wound repair and subsequent scar formation. Fibroblasts undergo apoptosis as granulation tissue evolves into a scar. To determine whether TGF-beta influences fibroblast apoptosis, human lung fibroblasts (IMR-90) were treated with TGF-beta (2 to 10 ng/mL) and then exposed to H(2)O(2) (50 to 150 microM), an inducer of fibroblast apoptosis. Apoptosis was evaluated by nuclear staining with Hoechst33342 and terminal deoxynucleotidyl transferase (TdT)-mediated nucleotide nick-end labeling. TGF-beta alone did not induce fibroblast apoptosis, but it dose-dependently augmented the apoptosis induced by exposure to H(2)O(2). TGF-beta also increased the intracellular level of peroxides measured with carboxydichlorodihydrofluorescein, but it did not affect the protein levels of Bcl-2, Bax, Bad, or p53 proteins. These results suggest that TGF-beta promotes lung fibroblast apoptosis induced by H(2)O(2), probably by increasing intracellular peroxides. Thus, TGF-beta may promote the elimination of fibroblasts from wounds, particularly under conditions of exposure to enhanced oxidative stress in the lung.