title: Transforming growth factor-beta promotes fibroblast apoptosis induced by H2O2.
abstract: 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.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Yasuda
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide