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.
Highlights
Type I collagen is the primary structural protein in dermal extracellular matrix (ECM)
Solar UV Irradiation Stimulates Decorin Degradation in Human skin in vivo Sun-protected human buttock skin was exposed to two-times minimal erythema dose (MED) of solar-simulated UV irradiation, and full-thickness skin samples were obtained at baseline, 8 hours and 24 hour intervals for four days following UV irradiation (Fig. 1)
Proteoglycans and other soluble proteins were extracted from skin samples and were analyzed by Western blot analysis using an antibody against C-terminal region of decorin core protein
Summary
Type I collagen is the primary structural protein in dermal extracellular matrix (ECM). Solar ultraviolet (UV) irradiation induces proteolytic cleavage of type I collagen fibrils, which impairs skin structural integrity and function, and contributes to clinical features that are commonly observed in chronically sunexposed skin [1,2]. Acute UV irradiation dramatically increases de novo production of MMP-1 in skin resident cells [1,2]. MMP-1 initiates collagen degradation by cleaving a single site near the Cterminal end of type I collagen fibrils; this cleavage creates characteristic ‘‘1/4’’ length and ‘‘3/4’’ length collagen fragments. Collagen fragments generated by MMP-1 undergo further degradation by other MMPs. MMP-1 activity is a key modulator of dermal ECM degradation and is a potential therapeutic target to lessen photodamage [3,4]
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