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.

Increased fibroblast proliferation and activity after applying intense pulsed light 800–1200nm

“…Some authors have reported differences in decorin distribution (Ito et al, 2001), increased levels after UVA radiation (Kawashima et al, 2006), decreased levels after solar ultraviolet irradiation (Gambichler et al, 2007;Li et al, 2013a), or decreased levels in aged skin in vivo (Oh et al, 2011). In the present study, no significant changes in decorin expression have been found and this observation is in agreement with previous data that demonstrate human skin decorin minimal age-related differences (Carrino et al, 2011) and changes in decorin molecular size in aged skin which is significantly smaller than in young skin (Li et al, 2013b).…”

Intense pulsed light induces synthesis of dermal extracellular proteins in vitro

“…No significant changes have been observed in cell lysates, which could be explained because decorin is synthesized and immediately expulsed to ECM. This results contrast with previous data that demonstrate human skin decorin minimal age-related differences [4] and changes in decorin molecular size in aged skin where is significantly smaller than in young skin [53]. So, clearly, new experiments are necessary to elucidate the role of the decorin in dermis.…”

Glycosaminoglycan and proteoglycan in skin aging

“…The intact form of decorin (70-100 kDa) is composed of a 45-kDa core protein with 1 DS chain at Ser4 [15,19,20], and proteolytic fragment forms are observed in the adult dermis [32,33]. The intact form of biglycan (~240 kDa) is composed of a 40-kDa core protein with 2 DS chains at Ser42 and Ser47, and the monoglycosylated form (70-100 kDa) is detected in the human skin [19] or in cultured dermal fibroblasts [15].…”

“…The intact form of biglycan (~240 kDa) is composed of a 40-kDa core protein with 2 DS chains at Ser42 and Ser47, and the monoglycosylated form (70-100 kDa) is detected in the human skin [19] or in cultured dermal fibroblasts [15]. They bind to several types of collagens and elastic fiber components to regulate their fibrillogenesis [15,21,33]. Decorin-knockout mice exhibited thin and fragile skin with reduced tensile strength (dermatosparaxis-like phenotype) caused by irregular collagen fibrillogenesis [34].…”