S-Nitroso-N-acetylcysteine induces de-differentiation of activated hepatic stellate cells and promotes antifibrotic effects in vitro

Autor(es)

Stefano, J. T. ^[1] ; Cogliati, B. ^[1] ; Santos, F. ^[2] ; Lima, V. M. R. ^[1] ; Mazo, D. C. ^[1] ; Matte, U. ^[2] ; Alvares-da-Silva, M. R. ^[2] ; Silveira, T. R. ^[2] ; Carrilho, F. J. ^[1] ; Oliveira, C. P. M. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Gastroenterol LIM 07, BR-01246903 Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Sul, Dept Internal Med & Pediat, Hosp Clin Porto Alegre, Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 25, n. 3, p. 360-365, OCT 30 2011.
• Citações Web of Science: 8

Resumo

Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100 mu M) or vehicle (control group) for 72 h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGF beta-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGF beta-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis. (C) 2011 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 08/56157-7 - Aspectos fisiopatogênicos e terapêuticos da fibrogênese e carcinogênese hepática experimental na doença hepática gordurosa não alcoólica: avaliação do efeito de doadores de óxido nítrico in vitro
• Beneficiário: Claudia Pinto Marques Souza de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores