Age-associated decrease in GDNF and its cognate receptor GFR-1 protein expression in human skin

作者:Adly Mohamed A; Assaf Hanan A; Hussein Mahmoud Rezk Abdelwahed*
来源:International Journal of Experimental Pathology, 2016, 97(3): 248-256.
DOI:10.1111/iep.12175

摘要

Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFR-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that GDNF and GFR-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18years), adults (19-60years) and the elderly (61-81years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFR-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFR-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFR-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFR-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFR-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFR-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations.

  • 出版日期2016-6

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