Abstract
The turnover of the epidermis beginning with the progenitor cells in the basal layer to the fully differentiated corneocytes is tightly regulated by calcium. Calcium more than anything else promotes the differentiation of keratinocytes which implies the need for a calcium gradient with low concentrations in the stratum basale and high concentrations in the stratum granulosum. One of the hallmarks of skin aging is a collapse of this gradient that has a direct impact on the epidermal fitness. The rise of calcium in the stratum basale reduces cell proliferation, whereas the drop of calcium in the stratum granulosum leads to a changed composition of the cornified envelope. We showed that keratinocytes respond to the calcium induced block of cell division by a large increase of the expression of several miRNAs (hsa-mir542-5p, hsa-mir125a, hsa-mir135a-5p, hsa-mir196a-5p, hsa-mir491-5p and hsa-mir552-5p). The pitfall of this rescue mechanism is a dramatic change in gene expression which causes a further impairment of the epidermal barrier. This effect is attenuated by a pseudogene (SPRR2C) that gives rise to a lncRNA. SPRR2C specifically resides in the stratum granulosum/corneum thus acting as a sponge for miRNAs.
Highlights
The aging process is to a large part still enigmatic
In this paper we are not considering factors that contribute to the breakdown of the epidermal calcium gradient, but we demonstrate how the epidermis adapts to the altered calcium levels in each stratum by the expression of long non-coding RNA (lncRNA) and miRNAs
In healthy epidermis a calcium gradient is established. This is of absolute necessity because Ca2+ is essential for differentiation of keratinocytes and detrimental to progenitor cells
Summary
The aging process is to a large part still enigmatic. This is attributed to the fact that aging is multifactorial and is dependent on such processes as senescence, loss of proteostasis, changes on the epigenetic level, altered mitochondrial functions and many more (reviewed in [1]). If a hallmark of an aged dermis has to be named, it is the changed architectural organization of the extracellular matrix, resulting www.aging-us.com in folds and wrinkles. Increased UVexposure ( ́photoaging) results in increased ROS levels that stimulates the activation of matrix metalloproteases leading to an increased turnover of the extracellular matrix [2]
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