title: Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin.
abstract: Punch biopsies of human skin were obtained 1 day after irradiation with two minimal-erythema doses (MED) from either a UVB light source or a Solar Simulator and incubated in organ culture for 72 h. Organ culture fluids obtained at 24, 48 and 72 h were analyzed for collagenolytic activity and for reactivity with antibodies to matrix metalloproteinase-1 (MMP-1; interstitial collagenase) and MMP-13 (collagenase-3). High levels of collagenolytic activity were seen in organ culture fluid from skin exposed to either light source. MMP-1 was strongly induced in parallel, increasing from less than 100 ng/ml in organ culture fluid from control skin to approximately 1.1 microg/ml in culture fluid from UV-treated skin. Whereas most of the detectable MMP-1 in control culture fluid was represented by the latent form of the enzyme, approximately 50% of the enzyme was present as the active form in organ culture fluid of UV-exposed skin. In contrast, there was no detectable MMP-13 in control organ culture fluid and very little change after UV exposure (less than 100 ng/ml in both cases). Finally, neutralization studies with a blocking antibody to MMP-1 removed 95 +/- 4% of the collagenolytic activity in the organ culture fluid from UV-treated skin. These findings strongly implicate MMP-1 rather than MMP-13 as the major collagenolytic enzyme responsible for collagen damage in photoaging.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Brennan
authors.forename: Humaa
authors.initials: H
authors.lastname: Bhatti
authors.forename: Kamalakar C
authors.initials: KC
authors.lastname: Nerusu
authors.forename: Narasimharao
authors.initials: N
authors.lastname: Bhagavathula
authors.forename: Sewon
authors.initials: S
authors.lastname: Kang
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
authors.forename: James
authors.initials: J
authors.lastname: Varani
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000328:Adult; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000528:radiation effects; D017364:Collagenases / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism / Q000502:physiology*; D053509:Matrix Metalloproteinase 13; D008875:Middle Aged; D009924:Organ Culture Techniques; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D015595:Skin Aging; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: D003094:Collagen; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1