title: Solar ultraviolet irradiation induces decorin degradation in human skin likely via neutrophil elastase.
abstract: Exposure of human skin to solar ultraviolet (UV) irradiation induces matrix metalloproteinase-1 (MMP-1) activity, which degrades type I collagen fibrils. Type I collagen is the most abundant protein in skin and constitutes the majority of skin connective tissue (dermis). Degradation of collagen fibrils impairs the structure and function of skin that characterize skin aging. Decorin is the predominant proteoglycan in human dermis. In model systems, decorin binds to and protects type I collagen fibrils from proteolytic degradation by enzymes such as MMP-1. Little is known regarding alterations of decorin in response to UV irradiation. We found that solar-simulated UV irradiation of human skin in vivo stimulated substantial decorin degradation, with kinetics similar to infiltration of polymorphonuclear (PMN) cells. Proteases that were released from isolated PMN cells degraded decorin in vitro. A highly selective inhibitor of neutrophil elastase blocked decorin breakdown by proteases released from PMN cells. Furthermore, purified neutrophil elastase cleaved decorin in vitro and generated fragments with similar molecular weights as those resulting from protease activity released from PMN cells, and as observed in UV-irradiated human skin. Cleavage of decorin by neutrophil elastase significantly augmented fragmentation of type I collagen fibrils by MMP-1. Taken together, these data indicate that PMN cell proteases, especially neutrophil elastase, degrade decorin, and this degradation renders collagen fibrils more susceptible to MMP-1 cleavage. These data identify decorin degradation and neutrophil elastase as potential therapeutic targets for mitigating sun exposure-induced collagen fibril degradation in human skin.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Remmer
authors.forename: John
authors.initials: J
authors.lastname: Voorhees
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
mesh_terms: D000328:Adult; D058575:Decorin / Q000378:metabolism*; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000528:radiation effects; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D059748:Proteolysis / Q000528:radiation effects*; D012867:Skin / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D058575:Decorin; D024022:Fibrillar Collagens; D019272:Leukocyte Elastase; D020781:Matrix Metalloproteinase 1
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