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

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art_STEFANO_SNitrosoNacetylcysteine_induces_dedifferentiation_of_activated_hepatic_stellate_cells_2011.PDF (451.76 KB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2011
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS INC ELSEVIER SCIENCE
Autores
COGLIATI, B.
SANTOS, F.
MATTE, U.
ALVARES-DA-SILVA, M. R.
SILVEIRA, T. R.
Citação
NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v.25, n.3, p.360-365, 2011
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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.
Palavras-chave
S-Nitroso-N-acetylcysteine, Fibrogenesis, Hepatic stellate cells
URI
https://observatorio.fm.usp.br/handle/OPI/23004
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MGT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/07