Reduced expression of Collagen 17A1 in naturally aged, photoaged, and UV-irradiated human skin in vivo: Potential links to epidermal aging

Abstract

Collagen 17A1 (COL17A1) is atransmembrane structural component of the hemidesmosome that mediate adhesion of keratinocytes to the underlying membrane. Recent work in mouse showed that COL17A1 deficiency leads to premature skin aging. Although the role COL17A1 in skin aging is becoming recognized in mouse models, its connection to human skin natural aging/photoaging/ultraviolet (UV)-irradiated human skin has received little attention. To determine COL17A1 expression in naturally aged and photoaged as well as acutely UV irradiated human skin, skin samples were obtained from: (1) young (N = 10, 26.7±1.3 years) and aged (N = 10, 84.0 ± 1.7 years) sun-protected buttock skin; (2) photoaged extensor forearm and subject matched sun-protected underarm skin (N = 6, 56.0 ± 3.4 years); (3) solar-simulated UV-irradiated buttock skin (N = 6, 51.2 ± 3.6 years). COL17A1 levels were determined by immunohistology and RT-PCR, and the potential role of COL17A1 in epidermal aging was investigated by immunostaining of the marker for interfollicular epidermal stem cells and keratinocytes proliferation. We found that COL17A1 is specifically expressed in interfollicular epidermal stem cell niches, and that significantly reduced in naturally aged, photoaged, and acute UV-irradiated human skin in vivo. COL17A1 is identified as keratinocyte-specific collagen, and UV irradiation significantly downregulates COL17A1 expression in keratinocytes. Reduced expression of COL17A1 is positively correlated with impaired regeneration of keratinocytes and reduced dermal-epidermal junction as well as thin epidermis in aged human skin (epidermal aging). We also confirmed that keratinocyte-specific integrin β4 (ITGB4), which interacts with COL17A1, is reduced in aged human skin. Mechanistically, we found that matrix metalloproteinases (MMPs) are responsible for UV-mediated COL17A1 degradation in both in vitro keratinocytes and in vivo mouse skin. These data suggest the possible links between reduced expression of COL17A1 and epidermal aging in human skin.