title: Retinoic acid receptor alpha expression and cutaneous ageing.
abstract: Intrinsic ageing of human skin is a subtle and gradual process that demonstrates few clinical or histological features until old age (>70 years). Initial work indicates that aged skin is "retinoid sensitive" but there is little data on the role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin ageing. As nuclear retinoid receptors have been implicated in ageing in rodents, we studied the distribution of these receptors in intrinsically aged as compared to young, photoprotected human skin. We found that intrinsic ageing of skin in vivo is accompanied by significant increases of RAR alpha mRNA and protein whereas other isoforms show no alteration with age. In vitro transfection of COS-1 cells with the RAR alpha gene induces expression of matrix metalloproteinase-1 (MMP-1), an enzyme known to play an active role in remodelling of the dermis in intrinsically aged and photoaged skin. Furthermore, addition of all-trans retinoic acid (RA) to cultures of RAR alpha-transfected COS-1 cells diminishes RAR alpha and returns levels of MMP-1 to those approaching baseline. These results demonstrate that intrinsic ageing of human skin is accompanied by significant elevation in the content of RAR alpha and that over-expression of RAR alpha influences expression of MMP-1, an important mediator of skin ageing.
authors.affiliation: Dermatopharmacology Unit, Dermatology Centre, University of Manchester, Irving Building, Hope Hospital, Salford, Manchester M6 8HD, UK.
authors.forename: Rachel E B
authors.initials: RE
authors.lastname: Watson
authors.forename: J
authors.initials: J
authors.lastname: Arjuna Ratnayaka
authors.forename: Rebecca C C
authors.initials: RC
authors.lastname: Brooke
authors.forename: Sharon
authors.initials: S
authors.lastname: Yee-Sit-Yu
authors.forename: Philippe
authors.initials: P
authors.lastname: Ancian
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells / Q000187:drug effects; D016922:Cellular Senescence / Q000502:physiology; D002522:Chlorocebus aethiops; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D015595:Skin Aging / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D018840:HSP70 Heat-Shock Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D020781:Matrix Metalloproteinase 1