Abstract
The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes.
Highlights
Skin constitutes the protective barrier of the body and mediates its interaction with the environment
We examined the expression profile of perlecan during chronological skin aging and showed that its expression decreased over time
Our QPCR analysis revealed a reduced level of perlecan transcripts in aging keratinocytes, which suggested that www.impactaging.com www.impactaging.com disturbing the ability to neo-synthesize perlecan may create a disorder in the perlecan synthesis/degradation balance
Summary
Skin constitutes the protective barrier of the body and mediates its interaction with the environment. A highly specialized extracellular matrix (ECM) named dermal epidermal junction (DEJ) separates the epidermal and dermal compartments. The epidermis, primarily made of keratinocytes, is continuously renewed by the proliferation of stem cells and the differentiation of their progeny, which undergo terminal differentiation as they leave the basal layer and move upward toward the surface, where they die and slough off [1]. Basal keratinocytes append the DEJ, a cell surface-associated extracellular matrix that forms as a concerted action of both epidermal and dermal cells [2]. The DEJ provides both a structural support to keratinocytes and a specific niche that mediates signals influencing their behaviour. Similar to all basement membranes (BMs), the DEJ primarily consists of laminins, type IV collagen, nidogens, and the heparan sulfate proteoglycan (HSPG)
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