Perlecan expression influences the keratin 15-positive cell population fate in the epidermis of aging skin

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,...

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Bibliographic Details
Published in:Aging (Albany, NY.) NY.), 2016-04, Vol.8 (4), p.751-768
Main Authors: Dos Santos, Morgan, Michopoulou, Anna, André-Frei, Valérie, Boulesteix, Sophie, Guicher, Christine, Dayan, Guila, Whitelock, John, Damour, Odile, Rousselle, Patricia
Format: Article
Language:English
Subjects:
Adult
Aged
Bioengineering
Biomaterials
Cell Differentiation - physiology
Cellular Biology
Epidermis - cytology
Epidermis - metabolism
Extracellular Matrix - metabolism
Female
Heparan Sulfate Proteoglycans - metabolism
Humans
Keratin-15 - metabolism
Keratinocytes - cytology
Keratinocytes - metabolism
Life Sciences
Male
Middle Aged
Research Paper
Skin Aging - physiology
Young Adult
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.100928