Abstract

Daily sunlight exposure damages the epidermal basement membrane (BM) and disrupts epidermal homeostasis. Inter-follicular epidermal stem cells (IFE-SCs) regulate epidermal proliferation and differentiation, which supports epidermal homeostasis. Here, we examine how photoaging affects the function of IFE-SCs and we identify key components in their cellular environment (niche). We found that sun-exposed skin showed a decrease of MCSP-positive and β1-integrin-positive cells concomitantly with a decrease of laminin-511 at the dermal–epidermal junction (DEJ), as compared with sun-protected skin. Higher levels of laminin-511 were associated with not only increased efficiency of colony formation, but also higher expression levels of MCSP as well as other stem cell markers such as Lrig1, ITGB1, CD44, CD46, DLL1, and K15 in keratinocytes from skin of 12- to 62-year-old subjects. UVB exposure to cultured human skin impaired laminin-511 integrity at the dermal–epidermal junction and reduced MCSP-positive basal epidermal cells as well as K15-positive cells. Combined treatment with matrix metalloproteinase and heparanase inhibitors protected the integrity of laminin-511 and inhibited the reduction of MCSP-positive cells and K15-positive cells. These results suggest that photoaging may reduce the levels of MCSP-positive and K15-positive epidermal stem/progenitor cells in the epidermis via loss of laminin-511 at the dermal–epidermal junction.

Highlights

  • Sunlight exposure damages the epidermal basement membrane (BM) and disrupts epidermal homeostasis

  • We have shown that matrix metalloproteinases (MMPs) and heparanase are activated in UVB-irradiated human ­skin[27,28], and that UV-damaged BM structure is reconstituted in the presence of inhibitors of MMPs and heparanase, concomitantly with the induction of epidermal differentiation markers such as filaggrin, loricrin, and bleomycin hydrolase in the granular layer of the ­epidermis[28]

  • Since decreased levels of laminin-511 and α6β1 integrin during aging in sun-exposed skin were associated with the reduction of MCSPpositive epidermal stem cells, we examined whether laminin-511 could reduce the loss of inter-follicular epidermal stem/progenitor cells by means of a colony formation assay on laminin-511-coated plates

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Summary

Introduction

Sunlight exposure damages the epidermal basement membrane (BM) and disrupts epidermal homeostasis. Combined treatment with matrix metalloproteinase and heparanase inhibitors protected the integrity of laminin-511 and inhibited the reduction of MCSP-positive cells and K15-positive cells These results suggest that photoaging may reduce the levels of MCSP-positive and K15-positive epidermal stem/ progenitor cells in the epidermis via loss of laminin-511 at the dermal–epidermal junction. Abbreviations TEWL Transepidermal water loss MMP(s) Matrix metalloproteinase(s) UVB Ultraviolet B HS Heparan sulfate MCSP Melanoma-associated chondroitin sulphate proteoglycan DEJ Dermal–epidermal junction IFE-SCs Interfollicular epidermal stem cells BM Basement membrane SE Skin equivalent. Interfollicular epidermal stem cells (IFE-SCs) play an especially important role in epidermal homeostasis under normal c­ onditions[3] These cells express high levels of α6 and β1 i­ntegrins[4,5], but lower levels of transferrin receptor C­ D716. It is not clear whether sunlight exposure influences the age-dependent change of laminins in the skin

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