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Matrix Metalloproteinase‐1 is the Major Collagenolytic Enzyme Responsible for Collagen Damage in UV‐irradiated Human Skin ¶
Author(s) -
Brennan Meghan,
Bhatti Humaa,
Nerusu Kamalakar C.,
Bhagavathula Narasimharao,
Kang Sewon,
Fisher Gary J.,
Varani James,
Voorhees John J.
Publication year - 2003
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2003)0780043mmitmc2.0.co2
Subject(s) - organ culture , collagenase , matrix metalloproteinase , human skin , interstitial collagenase , enzyme , erythema , chemistry , matrix (chemical analysis) , metalloproteinase , photoaging , body fluid , pathology , biochemistry , biology , immunology , medicine , dermatology , in vitro , chromatography , genetics
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 mg/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.