title: Aging decreases collagen IV expression in vivo in the dermo-epidermal junction and in vitro in dermal fibroblasts: possible involvement of TGF-β1.
abstract: Collagen IV is a major component of the dermo-epidermal junction (DEJ). To study expression of collagen IV upon aging in the DEJ and dermal fibroblasts isolated from the same patients. A model of senescent fibroblasts was developed in order to identify biological compounds that might restore the level of collagen IV. Skin fragments of women (30 to 70 years old) were collected. Localisation of collagen IV expression in the DEJ was studied by immunofluorescence. Fibroblast collagen IV expression was studied by real-time PCR, ELISA, and western blotting. Premature senescence was simulated by exposing fibroblasts to subcytotoxic H2O2 concentrations. Collagen IV decreased in the DEJ and fibroblasts relative to age. TGF-β1 treatment significantly increased collagen IV gene and protein expression in fibroblasts and restored expression in the model of senescence. Addition of TGF-β1-neutralizing antibody to fibroblast cultures decreased collagen IV expression. Taken together, the results suggest that the decrease in collagen IV in the DEJ, relative to age, could be due to a decrease in collagen IV expression by senescent dermal fibroblasts and may involve TGF-β1 signalling.
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095.
authors.forename: Jezabel
authors.initials: J
authors.lastname: Feru
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095.
authors.forename: Etienne
authors.initials: E
authors.lastname: Delobbe
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095, Laboratoire Central de Biochimie, Hôpital Robert Debré, CHU de Reims, Avenue du Général Koenig, 51092.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ramont
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Brassart
authors.affiliation: Plate-forme d'Imagerie Cellulaire et Tissulaire IBISA, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095.
authors.forename: Christine
authors.initials: C
authors.lastname: Terryn
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Dupont-Deshorgue
authors.affiliation: Départements de Biopathologies, Institut Jean-Godinot-Unicancer, 1 rue du général KOENIG CS80014 51726 Reims Cedex, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Garbar
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095, Laboratoire Central de Biochimie, Hôpital Robert Debré, CHU de Reims, Avenue du Général Koenig, 51092.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Monboisse
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095, Laboratoire Central de Biochimie, Hôpital Robert Debré, CHU de Reims, Avenue du Général Koenig, 51092.
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Maquart
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS UMR 7369: Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq Jay, CS 30018, 51095.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brassart-Pasco
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology*; D001485:Basement Membrane / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D024141:Collagen Type IV; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: TGF-β1; collagen IV; dermo-epidermal junction; fibroblast; skin; stress-induced premature senescence