BACKGROUND/AIMS: Hepatic stellate cells (HSC) are liver-specific pericytes implicated in liver tissue repair. Activation of signaling pathways in HSC modulates hepatic fibrogenesis, but no information is available on the possible role of ERK5, a member of the mitogen-activated protein kinase family, in this process. In this study, we investigated the role of ERK5 in the biologic responses triggered by platelet-derived growth factor (PDGF) in HSC. METHODS: Human HSC were cultured on plastic and studied in their myofibroblast-like phenotype. RESULTS: PDGF-BB rapidly induced ERK5 activation and translocation to the nucleus. EGF and PDGF-DD were also found to activate ERK5. Interfering with Src activation blocked PDGF-BB-dependent ERK5 phosphorylation. To establish the biological significance of ERK5 activation, HSC were transfected with non-targeting siRNA or siRNA targeting ERK5. ERK5 silencing inhibited PDGF-BB-induced cell proliferation, and expression and activation of c-Jun. In contrast, depletion of ERK5 was associated with significantly increased cell migration, both in the presence or absence of PDGF-BB. This effect was associated with a redistribution of focal contacts, and with decreased phosphorylation of FAK, paxillin, and PAK. CONCLUSIONS: ERK5 modulates PDGF-dependent biologic activities in human HSC, generating positive signals for cell proliferation downregulating the ability of the cells to migrate.

ERK5 differentially regulates PDGF-induced proliferation and migration of hepatic stellate cells / E.Rovida; N.Navari; A.Caligiuri; P.Dello Sbarba; F.Marra. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - STAMPA. - 48:(2008), pp. 107-115. [10.1016/j.jhep.2007.08.010]

ERK5 differentially regulates PDGF-induced proliferation and migration of hepatic stellate cells.

ROVIDA, ELISABETTA;DELLO SBARBA, PERSIO;MARRA, FABIO
2008

Abstract

BACKGROUND/AIMS: Hepatic stellate cells (HSC) are liver-specific pericytes implicated in liver tissue repair. Activation of signaling pathways in HSC modulates hepatic fibrogenesis, but no information is available on the possible role of ERK5, a member of the mitogen-activated protein kinase family, in this process. In this study, we investigated the role of ERK5 in the biologic responses triggered by platelet-derived growth factor (PDGF) in HSC. METHODS: Human HSC were cultured on plastic and studied in their myofibroblast-like phenotype. RESULTS: PDGF-BB rapidly induced ERK5 activation and translocation to the nucleus. EGF and PDGF-DD were also found to activate ERK5. Interfering with Src activation blocked PDGF-BB-dependent ERK5 phosphorylation. To establish the biological significance of ERK5 activation, HSC were transfected with non-targeting siRNA or siRNA targeting ERK5. ERK5 silencing inhibited PDGF-BB-induced cell proliferation, and expression and activation of c-Jun. In contrast, depletion of ERK5 was associated with significantly increased cell migration, both in the presence or absence of PDGF-BB. This effect was associated with a redistribution of focal contacts, and with decreased phosphorylation of FAK, paxillin, and PAK. CONCLUSIONS: ERK5 modulates PDGF-dependent biologic activities in human HSC, generating positive signals for cell proliferation downregulating the ability of the cells to migrate.
2008
48
107
115
E.Rovida; N.Navari; A.Caligiuri; P.Dello Sbarba; F.Marra
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/345980
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