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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis
Authors: Santiago, B. (Begoña)
Gutierrez-Cañas, I. (Irene)
Dotor, J. (Javier)
Palao, G. (Guillermo)
Lasarte, J.J. (Juan José)
Ruiz, J. (Juan)
Prieto, J. (Jesús)
Borras-Cuesta, F. (Francisco)
Pablos, J.L. (José L.)
Keywords: Antagonists
Fibrosis
Skin
Topical administration
Transforming growth factor beta
Issue Date: 2005
Publisher: Nature Publishing Group
Publisher version: http://www.nature.com/jid/journal/v125/n3/full/5603510a.html
ISSN: 1523-1747
Citation: Santiago B, Gutierrez-Canas I, Dotor J, Palao G, Lasarte JJ, Ruiz J, et al. Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. J Invest Dermatol 2005 Sep;125(3):450-455.
Abstract
Transforming growth factor-beta (TGF-beta) plays a crucial role in the pathogenesis of skin fibrotic diseases. Systemic TGF-beta inhibitors effectively inhibit fibrosis in different animal models; however, systemic inhibition of TGF-beta raises important safety issues because of the pleiotropic physiological effects of this factor. In this study, we have investigated whether topical application of P144 (a peptide inhibitor of TGF-beta1) ameliorates skin fibrosis in a well-characterized model of human scleroderma. C3H mice received daily subcutaneous injections of bleomycin for 4 wk, and were treated daily with either a lipogel containing P144 or control vehicle. Topical application of P144 significantly reduced skin fibrosis and soluble collagen content. Most importantly, in mice with established fibrosis, topical treatment with P144 lipogel for 2 wk significantly decreased skin fibrosis and soluble collagen content. Immunohistochemical studies in P144-treated mice revealed a remarkable suppression of connective tissue growth factor expression, fibroblast SMAD2/3 phosphorylation, and alpha-smooth muscle actin positive myofibroblast development, whereas mast cell and mononuclear cell infiltration was not modified. These data suggest that topical application of P144, a peptide inhibitor of TGF-beta1, is a feasible strategy to treat pathological skin scarring and skin fibrotic diseases for which there is no specific therapy.
Permanent link: http://hdl.handle.net/10171/21716
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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