S-Nitroso-N-acetylcysteine induces de-differentiation of activated hepatic stellate cells and promotes antifibrotic effects in vitro
| Autor: | José Tadeu Stefano, Ursula da Silveira Matte, F. Santos, Mário Reis Álvares-da-Silva, Claudia P. Oliveira, Bruno Cogliati, D.C. Mazo, Themis Reverbel da Silveira, Flair José Carrilho, V. M. R. Lima |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Liver Cirrhosis
Cancer Research Cell type Pathology medicine.medical_specialty Cell Survival Physiology Clinical Biochemistry Biology Biochemistry Nitric oxide Mice chemistry.chemical_compound Fibrosis Gene expression Hepatic Stellate Cells medicine Animals Viability assay Cells Cultured Dose-Response Relationship Drug Cell Dedifferentiation medicine.disease Acetylcysteine Cell biology chemistry Cell culture Hepatic stellate cell Myofibroblast |
| Zdroj: | Nitric Oxide. 25:360-365 |
| ISSN: | 1089-8603 |
| Popis: | 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 (100μM) or vehicle (control group) for 72h. 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. TGFβ-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 TGFβ-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect