title: MicroRNA-152 and -181a participate in human dermal fibroblasts senescence acting on cell adhesion and remodeling of the extra-cellular matrix.
abstract: Ageing of human skin is associated with phenotypic changes in the cutaneous cells; the major functional markers of ageing occur as consequences of dermal and epidermal cell senescence and of structural and compositional remodeling of normally long-lived dermal extracellular matrix proteins. Understanding the contribution of the dermal cells in skin ageing is a key question, since this tissue is particularly important for skin integrity and its properties can affect the epidermis. Several microRNAs have been shown to be involved in the regulation of pathways involved in cellular senescence and exerted important effects on tissues ageing. In this study, we demonstrate that the expression of miR-152 and miR-181a increased during the human dermal fibroblasts senescence and that their overexpression, is sufficient to induce cellular senescence in early-passage cells. The increase of these miRNAs during cells senescence was accompanied by a decrease in integrin α5 and collagen XVI expression at mRNA and/or protein levels resulting in reduced cellular adhesion and suggesting extracellular matrix remodeling. These findings indicate that changes in miRNAs expression, by modulating the levels of adhesion proteins and extra-cellular matrix components, such as integrin α5 and collagen XVI, could contribute to the compositional remodelling of the dermis and epidermis occurring during skin aging.
authors.affiliation: University of Tor Vergata, Department of Experimental Medicine and Surgery, 00133 Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Mancini
authors.forename: Gaelle
authors.initials: G
authors.lastname: Saintigny
authors.forename: Christian
authors.initials: C
authors.lastname: Mahé
authors.forename: Margherita
authors.initials: M
authors.lastname: Annicchiarico-Petruzzelli
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.forename: Eleonora
authors.initials: E
authors.lastname: Candi
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology; D014162:Transfection
chemical_list: C481130:COL16A1 protein, human; D039564:Integrin alphaV; C550856:MIRN152 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D003094:Collagen