• Open Access

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

Authors

  • Roberta Buonomo,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
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  • Ferdinando Giacco,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
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  • Angela Vasaturo,

    1. Department of Chemical Engineering, “Federico II” University of Naples, Naples, Italy
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  • Sergio Caserta,

    1. Department of Chemical Engineering, “Federico II” University of Naples, Naples, Italy
    2. CEINGE Biotecnologie Avanzate, Naples, Italy
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  • Stefano Guido,

    1. Department of Chemical Engineering, “Federico II” University of Naples, Naples, Italy
    2. CEINGE Biotecnologie Avanzate, Naples, Italy
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  • Valentina Pagliara,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
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  • Corrado Garbi,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
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  • Gelsomina Mansueto,

    1. Department of Biomorphological and Functional Sciences, “Federico II” University of Naples, Naples, Italy
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  • Angela Cassese,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
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  • Giuseppe Perruolo,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
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  • Francesco Oriente,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
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  • Claudia Miele,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
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  • Francesco Beguinot,

    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
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  • Pietro Formisano

    Corresponding author
    1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Naples, Italy
    2. Institute of Experimental Endocrinology and Oncology of CNR, Naples, Italy
    • Department of Cellular and Molecular Biology and Pathology, “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy.
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  • Disclosure of Potential Conflicts of Interest None.

  • Roberta Buonomo and Ferdinando Giacco contributed equally to this work.

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. Physiol. 227: 2106–2116, 2012. © 2011 Wiley Periodicals, Inc.

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