title: Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of IL-1β in chronically sun-exposed human skin.
abstract: Chronic exposure of human skin to solar ultraviolet (UV) irradiation causes premature skin aging, which is characterized by reduced type I collagen production and increased fragmentation of the dermal collagenous extracellular matrix. This imbalance of collagen homeostasis is mediated, in part, by elevated expression of the matricellular protein cysteine-rich protein 61 (CCN1), in dermal fibroblasts, the primary collagen producing cell type in human skin. Here, we report that the actions of CCN1 are mediated by induction of interleukin 1β (IL-1β). CCN1 and IL-1β are strikingly induced by acute UV irradiation, and constitutively elevated in sun-exposed prematurely aged human skin. Elevated CCN1 rapidly induces IL-1β, inhibits type I collagen production, and upregulates matrix metalloproteinase-1, which degrades collagen fibrils. Blockade of IL-1β actions by IL-1 receptor antagonist largely prevents the deleterious effects of CCN1 on collagen homeostasis. Furthermore, knockdown of CCN1 significantly reduces induction of IL-1β by UV irradiation, and thereby partially prevents collagen loss. These data demonstrate that elevated CCN1promotes inflammaging and collagen loss via induction of IL-1β and thereby contributes to the pathophysiology of premature aging in chronically sun-exposed human skin.
authors.affiliation: Department of Dermatology, University of Michigan Medical School, 1301, E. Catherine, Medical Science I, Room 6447, Ann Arbor, MI, 48109-5609, USA.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Qin
authors.forename: Toru
authors.initials: T
authors.lastname: Okubo
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
authors.forename: Taihao
authors.initials: T
authors.lastname: Quan
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015595:Skin Aging / Q000528:radiation effects*; D013472:Sunlight / Q000009:adverse effects*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; D055515:Cysteine-Rich Protein 61; D053583:Interleukin-1beta; D020781:Matrix Metalloproteinase 1