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

Autor: Ferdinando Giacco, Claudia Miele, Sergio Caserta, Angela Cassese, Francesco Beguinot, Pietro Formisano, Francesco Oriente, Corrado Garbi, Stefano Guido, Valentina Pagliara, Roberta Buonomo, Angela Vasaturo, Giuseppe Perruolo, Gelsomina Mansueto
Přispěvatelé: Buonomo, Roberta, Giacco, Ferdinando, Vasaturo, Angela, Caserta, Sergio, Guido, Stefano, Pagliara, Valentina, Garbi, Corrado, Mansueto, Gelsomina, Cassese, Angela, Perruolo, Giuseppe, Oriente, Francesco, Miele, Claudia, Beguinot, Francesco, Formisano, Pietro
Rok vydání: 2012
Předmět:
RHOA
Cytoskeleton organization
MAP Kinase Signaling System
Physiology
Clinical Biochemistry
Motility
Biology
Focal adhesion
Mice
03 medical and health sciences
0302 clinical medicine
Immune Regulation [NCMLS 2]
Cell Movement
Original Research Articles
Cell Adhesion
medicine
Extracellular
Animals
Humans
Cell adhesion
Fibroblast
Cells
Cultured
030304 developmental biology
Membrane transport and intracellular motility Translational research [NCMLS 5]
Flavonoids
Mice
Knockout
Mitogen-Activated Protein Kinase 1
0303 health sciences
Mitogen-Activated Protein Kinase 3
Animal
Histocompatibility Antigens Class I
Cell migration
Cell Biology
Fibroblasts
Phosphoproteins
Cell biology
medicine.anatomical_structure
Diabetes Mellitus
Type 2
Phosphoprotein
030220 oncology & carcinogenesis
Flavonoid
biology.protein
Apoptosis Regulatory Proteins
rhoA GTP-Binding Protein
Human
Zdroj: Journal of Cellular Physiology
Journal of Cellular Physiology; Vol 227
Journal of Cellular Physiology, 227, 5, pp. 2106-16
Journal of Cellular Physiology, 227, 2106-16
Journal of cellular physiology
(2012).
info:cnr-pdr/source/autori: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./titolo:PED%2FPEA-15 controls fibroblast motility and wound closure by ERK1%2F2-dependent mechanisms./doi:/rivista:Journal of cellular physiology (Print)/anno:2012/pagina_da:/pagina_a:/intervallo_pagine:/volume
ISSN: 1097-4652
0021-9541
DOI: 10.1002/jcp.22944
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: