title: ERK5 differentially regulates PDGF-induced proliferation and migration of hepatic stellate cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Dipartimento di Patologia e Oncologia Sperimentali, University of Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rovida
authors.forename: Nadia
authors.initials: N
authors.lastname: Navari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Caligiuri
authors.forename: Persio
authors.initials: P
authors.lastname: Dello Sbarba
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000502:physiology*; D020286:Pericytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D034741:RNA, Small Interfering; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D048054:Mitogen-Activated Protein Kinase 7