The effect of topical antitransforming growth factor-β1 in bleomycin-induced skin fibrosis in adult male albino rats: histological, immunohistochemical, and ultrastructural study

Background:Bleomycin is a frequently used antitumor antibiotic, effective against various kinds of malignancy. It was shown that transforming growth factor TGF)-β1 is a mediator of the fibrotic effect of bleomycin on skin constituted cells such as fibroblasts and endothelial cells. Peptide inhibitor, P144, has been specifically designed to block the interaction between TGF-β1 and its receptors. Aim of the work :The aim of this study was to demonstrate the histological changes in rat skin that might result from repeated local injections of bleomycin and to evaluate the efficacy of a topical application of anti-TGF-β1 on these changes. Material and methods:Thirty adult male albino rats were divided into three equal groups: a control group, a bleomycin-treated group, and a third group that was topically treated with a P144 lipogel emulsion (a peptide inhibitor of TGF-β1). Skin specimens were processed for light and electron microscopic studies. Paraffin sections were stained with H E, and anti-TGF-β1immunohistochemistry. Ultrathin sections were contrasted with uranyl acetate and lead citrate for ultrastructural study. The dermal thickness and fibroblast count were determined and the results were statistically analyzed. Results: There was a significant increase in dermal thickness characterized by thick collagen bundles and cellular infiltrates in the bleomycin-treated group, and immunohistochemical examination showed an increase in the number of TGF- β1-positive fibroblasts compared with that in the control group. Treatment with topical P144 exerted a profound effect by decreasing the number of fibroblasts and consequently attenuated the severity of dermal fibrosis. Conclusion:Inhibition of TGF-β1 signaling by a topical application of P144, a peptide inhibitor of TGF-β1, represents a novel approach to reduce and prevent bleomycin-induced skin fibrosis in adult male albino rats.