Activation of heparanase by ultraviolet B irradiation leads to functional loss of basement membrane at the dermal–epidermal junction in human skin

Abstract

Recently, we reported that heparanase plays important roles in barrier-disrupted skin, leading to increased interaction of growth factors between epidermis and dermis and facilitating various cutaneous changes, including epidermal hyperplasia and wrinkle formation. However, the role of heparanase in sun-exposed skin remains unknown. Here, we show that heparanase in human keratinocytes is activated by ultraviolet B (UVB) exposure and that heparan sulfate of perlecan is markedly degraded in UVB-irradiated human skin. The degradation of heparan sulfate resulted in a marked reduction of binding activity of the basement membrane for vascular endothelial growth factor, fibroblast growth factor-2 and -7 at the dermal-epidermal junction. Degradation of heparan sulfate was observed not only in acutely UVB-irradiated skin, but also in skin chronically exposed to sun. Interestingly, heparan sulfate was found to be degraded in sun-exposed skin, but not in sun-protected skin. These findings suggest that chronic UVB exposure activates heparanase, leading to degradation of heparan sulfate in the basement membrane and increased growth factor interaction between epidermis and dermis. These changes may facilitate photo-aging.

Hyperpigmentation in human solar lentigo is promoted by heparanase-induced loss of heparan sulfate chains at the dermal–epidermal junction

“…with reports of hyperpermeability and angiogenesis in papillary dermis of sun-exposed skin [34,36]. Computer-assisted analysis of CD31-stained sections revealed a 16.1% increase (P = 0.139) in vessel density (Fig.…”

“…It has been reported that heparanase in epidermis is activated by UVB exposure [34], and this is associated with angiogenesis and hyperpermeability of blood vessels in dermis [39]. In addition, upregulation of inflammation-related genes in solar lentigo lesions was revealed by means of gene expression profiling analysis [8,40].…”

“…Since heparanase is known to be induced and activated in epidermis of SE [38] and sun-exposed skin [34], we examined the role of heparanase in the pigmentation in pigmented SE by using a specific heparanase inhibitor, BIPBIPU, which has been shown to improve the deposition of HS and the basement membrane structure at the DEJ in SE [38]. The pigmented SEs were cultured with or without BIPBIPU (Fig.…”

“…In normal skin, heparanase is expressed in stratum corneum and hair inner root sheath, and may be involved in differentiation, desquamation and hair growth [30,31]. In inflammatory conditions, such as wound angiogenesis, wound healing and UVBirradiated skin, it is increased [32][33][34]. In addition, degradation of HS at the DEJ in photo-aged skin impairs the function of the basement membrane, which regulates transfer of several growth factors between epidermis and dermis [34].…”

“…In inflammatory conditions, such as wound angiogenesis, wound healing and UVBirradiated skin, it is increased [32][33][34]. In addition, degradation of HS at the DEJ in photo-aged skin impairs the function of the basement membrane, which regulates transfer of several growth factors between epidermis and dermis [34]. Heparanase is preferentially expressed in human tumors and its over-expression in tumor cells confers an invasive phenotype in experimental animals.…”