PED/PEA-15 controls fibroblast motility and wound closure by ERK1/2-dependent mechanisms

Roberta Buonomo, Ferdinando Giacco, Angela Vasaturo, Sergio Caserta, Stefano Guido, Valentina Pagliara, Corrado Garbi, Gelsomina Mansueto, Angela Cassese, Giuseppe Perruolo, Francesco Oriente, Claudia Miele, Francesco Beguinot, Pietro Formisano

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Cell migration is dependent on the control of signaling events that play significant roles in creating contractile force and in contributing to wound closure. We evaluated wound closure in fibroblasts from mice overexpressing (TgPED) or lacking ped/pea-15 (KO), a gene overexpressed in patients with type 2 diabetes. Cultured skin fibroblasts isolated from TgPED mice showed a significant reduction in the ability to recolonize wounded area during scratch assay, compared to control fibroblasts. This difference was observed both in the absence and in the presence of mytomicin C, an inhibitor of mitosis. In time-lapse experiments, TgPED fibroblasts displayed about twofold lower velocity and diffusion coefficient, as compared to controls. These changes were accompanied by reduced spreading and decreased formation of stress fibers and focal adhesion plaques. At the molecular level, TgPED fibroblasts displayed decreased RhoA activation and increased abundance of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ERK1/2 activity by PD98059 restored RhoA activation, cytoskeleton organization and cell motility, and almost completely rescued wound closure of TgPED fibroblasts. Interestingly, skin fibroblasts isolated from KO mice displayed an increased wound closure ability. In vivo, healing of dorsal wounds was delayed in TgPED and accelerated in KO mice. Thus, PED/PEA-15 may affect fibroblast motility by a mechanism, at least in part, mediated by ERK1/2. J. Cell.

Original languageEnglish (US)
Pages (from-to)2106-2116
Number of pages11
JournalJournal of Cellular Physiology
Volume227
Issue number5
DOIs
StatePublished - May 1 2012

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Buonomo, R., Giacco, F., Vasaturo, A., Caserta, S., Guido, S., Pagliara, V., Garbi, C., Mansueto, G., Cassese, A., Perruolo, G., Oriente, F., Miele, C., Beguinot, F., & Formisano, P. (2012). PED/PEA-15 controls fibroblast motility and wound closure by ERK1/2-dependent mechanisms. Journal of Cellular Physiology, 227(5), 2106-2116. https://doi.org/10.1002/jcp.22944