title: TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts.
abstract: BACKGROUND
  Transforming growth factor beta inducible early gene-1 (TIEG-1), a member of the Krüppel-like factor, was identified as a primary response gene for TGF-β. The role of TIEG-1 in skin repair has been mainly addressed in vivo on TIEG-1 null mice model and the mechanism remains unexplored.
  
  
  METHODS
  We investigated the modulation of TIEG-1 expression in normal human skin fibroblasts by either down-expressing or overexpressing the gene. We evaluated reactive oxygen species production and the cell viability of treated cells. The effect of TIEG-1 overexpression was monitored by wound healing assay and immunofluorescence staining of actin fibers organization and alpha-smooth muscle actin (α-SMA). Western blots were carried out to identify the level of expression or phosphorylation of key proteins such as cofilin, Rho GTPases, and p38 mitogen-activated protein kinase (p38 MAPK).
  
  
  RESULTS
  TIEG-1 down-regulation had a deleterious effect on the cell viability. It was significantly reduced (65±5%) and exposure to ultraviolet further increased this effect (47±3%). By contrast, cells overexpressing TIEG-1 had a reduced reactive oxygen species production (75%) compared to control and mock-transfected cells. This overexpression also resulted in formation of actin stress fibers and increased α-SMA expression and an enhanced wound healing feature. RhoB GTPase was upregulated and phosphorylation of cofilin and p38 MAPK was observed.
  
  
  CONCLUSIONS
  TIEG-1 overexpression in normal human skin fibroblasts results in improved resistance to oxidative stress, myofibroblast-like conversion that involved RhoB signaling pathway with cofilin and p38 MAPK proteins activation.
  
  
  CONCLUSIONS
  This study enlightens the role of TIEG-1 role in skin biology.
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, University of Orléans, Orléans, France.
authors.forename: Chloe
authors.initials: C
authors.lastname: Leduc
authors.affiliation: LVMH Recherche, 185 avenue de Verdun, Saint Jean de Braye, France.
authors.forename: Lauren
authors.initials: L
authors.lastname: Sobilo
authors.affiliation: I3MTO EA 4708, University of Orléans, Orléans, France.
authors.forename: Hechmi
authors.initials: H
authors.lastname: Toumi
authors.affiliation: Sederma, 29 Rue du Chemin Vert, 78610 Le Perray en Yvelines, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mondon
authors.affiliation: I3MTO EA 4708, University of Orléans, Orléans, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lespessailles
authors.affiliation: Inserm U930, Université de Tours, UFR Médecine, 2 Boulevard Tonnellé, 37044 Tours, France.
authors.forename: Fédéric
authors.initials: F
authors.lastname: Ossant
authors.affiliation: LVMH Recherche, 185 avenue de Verdun, Saint Jean de Braye, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Kurfurst
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, University of Orléans, Orléans, France. Electronic address: pichon@cnrs-orleans.fr.
authors.forename: Chantal
authors.initials: C
authors.lastname: Pichon
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D051765:Early Growth Response Transcription Factors / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D012867:Skin / Q000166:cytology; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cofilin; KLF10; Reactive oxygen species; Rho; SMA; TGF-β; TIEG-1; Wound healing