Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis.

HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2 / Granato, Marisa; Zompetta, C; Vescarelli, Enrica; Rizzello, C; Cardi, Antonio; Valia, S; Antonelli, Guido; Marchese, Cinzia; Torrisi, Maria Rosaria; Faggioni, Alberto; Cirone, Mara. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 6:30649(2016). [10.1038/srep30649]

HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

GRANATO, Marisa;Vescarelli, Enrica;CARDI, ANTONIO;ANTONELLI, Guido;MARCHESE, Cinzia;TORRISI, Maria Rosaria;FAGGIONI, Alberto;CIRONE, Mara
2016

Abstract

Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis.
GLI2 protein, human; nuclear protein; zinc finger protein GLI2
01 Pubblicazione su rivista::01a Articolo in rivista
HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2 / Granato, Marisa; Zompetta, C; Vescarelli, Enrica; Rizzello, C; Cardi, Antonio; Valia, S; Antonelli, Guido; Marchese, Cinzia; Torrisi, Maria Rosaria; Faggioni, Alberto; Cirone, Mara. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 6:30649(2016). [10.1038/srep30649]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/878547
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