title: UV-induced DNA damage initiates release of MMP-1 in human skin.
abstract: Destruction of collagen is a hallmark of photoaging. The major enzyme responsible for collagen 1 digestion, matrix metalloproteinase-1 (MMP-1), is induced by exposure to sunlight. To study the molecular trigger for this induction, human skin was ultraviolet-B (UVB)-irradiated and treated with liposome-encapsulated DNA repair enzymes. The photolyase-mediated DNA repair of epidermal UV damage was associated with a reduction of MMP-1 mRNA and protein expression in both the epidermal and dermal compartments of the skin. The role of the epidermal cells in MMP-1 induction in the fibroblasts was examined when human epidermal keratinocytes were irradiated with UVB and their media were transferred to unirradiated human dermal fibroblasts. Transfer of media from irradiated keratinocytes to unirradiated fibroblasts enhanced MMP-1 mRNA and protein. Thus, UV damage to keratinocytes of the epidermis may participate in the destruction of collagen in the dermis by release of soluble mediators that signal fibroblasts to release MMP-1. The MMP-1 induction was reduced when the keratinocytes were treated with DNA repair enzymes T4 endonuclease V or UV endonuclease prior to transfer of the media to fibroblasts. This implies that UVB, which deposits most of its energy on the chromatin of the epidermal keratinocytes and to a lesser extent in the upper dermis, has a significant role in photoaging. DNA damage in the keratinocytes initiates one of the signals for MMP-1 release, and enhancing DNA repair can reduce MMP-1 expression in human skin cells and tissue.
authors.affiliation: AGI Dermatics, Freeport, New York, USA.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Dong
authors.forename: Niusha
authors.initials: N
authors.lastname: Damaghi
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Picart
authors.forename: Nelli G
authors.initials: NG
authors.lastname: Markova
authors.forename: Kei
authors.initials: K
authors.lastname: Obayashi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Okano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Masaki
authors.forename: Susanne
authors.initials: S
authors.lastname: Grether-Beck
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Smiles
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Yarosh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002460:Cell Line; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology*; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000737:chemistry / Q000378:metabolism; D020405:Dermis / Q000378:metabolism / Q000528:radiation effects; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008081:Liposomes / Q000737:chemistry; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D055815:Young Adult
chemical_list: D008081:Liposomes; D009097:Multienzyme Complexes; D011740:Pyrimidine Dimers; D014764:Viral Proteins; C032219:UV endonuclease; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer); D020781:Matrix Metalloproteinase 1; D004255:Deoxyribodipyrimidine Photo-Lyase