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J Hepatol. 2008 Jan;48(1):107-15. Epub 2007 Oct 17.

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

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  • 1Dipartimento di Patologia e Oncologia Sperimentali, University of Florence, Italy.

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.

PMID:
17998143
[PubMed - indexed for MEDLINE]
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