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

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Abstract

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.

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