Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/74354
Type: Artigo de periódico
Title: Smad7 Blocks Transforming Growth Factor-beta 1-Induced Gingival Fibroblast-Myofibroblast Transition via Inhibitory Regulation of Smad2 and Connective Tissue Growth Factor
Author: Sobral, LM
Montan, PF
Zecchin, KG
Martelli, H
Vargas, PA
Graner, E
Coletta, RD
Abstract: Background: Transforming growth factor-beta 1 (TGF-beta 1), its downstream signaling mediators (Smad proteins), and specific targets, including connective tissue growth factor (CTGF), play important roles in tissue remodeling and fibrosis via myofibroblast activation. We investigated the effect of overexpression of Smad7, a TGF-beta 1 signaling inhibitor, on transition of gingival fibroblast to myofibroblast. Moreover, we analyzed the participation of CTGF on TGF-beta 1-mediated myofibroblast transformation. Methods: To study the inhibitory effect of Smad7 on TGF-beta 1/CTGF-mediating gingival fibroblast transition into myofibroblasts, we stably overexpressed Smad7 in normal gingival fibroblasts and in myofibroblasts from hereditary gingival fibromatosis (HGF). Myofibroblasts were characterized by the expression of the specific marker isoform alpha of the smooth muscle actin (alpha-SMA) by Western blot, flow cytometry, and immunofluorescence. Enzyme-linked immunosorbent assay for type I collagen was performed to measure myofibroblast activity. CTGF's role on myofibroblast transformation was examined by enzyme-linked immunosorbent assay and small interference RNA. Results: TGF-beta 1 induced the expression of alpha-SMA and CTGF, and small interference RNA-mediating CTGF silencing prevented fibroblast-myofibroblast switch induced by TGF-beta 1. In Smad7-overexpressing fibroblasts, ablation of TGF-beta 1-induced Smad2 phosphorylation marked decreased alpha-SMA, CTGF, and type I collagen expression. Similarly, HGF transfectants overexpressing Smad7 demonstrated low levels of alpha-SMA and phospho-Smad2 and significant reduction on CTGF and type I collagen production. Conclusions: CTGF is critical for TGF-beta 1-induced gingival fibroblast-myofibroblast transition, and Smad7 overexpression is effective in the blockage of myofibroblast transformation and activation, suggesting that treatments targeting myofibroblasts by Smad7 overexpression may be clinically effective in gingival fibrotic diseases, such as HGF. J Periodontol 2011;82:642-651.
Subject: Connective tissue growth factor
fibromatosis, gingiva
Smad2 protein
Smad7 protein
transforming growth factor-beta 1
Country: EUA
Editor: Amer Acad Periodontology
Rights: fechado
Identifier DOI: 10.1902/jop.2010.100510
Date Issue: 2011
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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