Research Paper Volume 13, Issue 15 pp 19127—19144
The life in a gradient: calcium, the lncRNA SPRR2C and mir542/mir196a meet in the epidermis to regulate the aging process
- 1 Procomcure Biotech, Breitwies, Thalgau, Austria
- 2 Department of Biosciences, Paris-Lodron University Salzburg, Salzburg, Austria
- 3 EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria
- 4 Department of Biosciences, Cancer Cluster Salzburg, Paris-Lodron University Salzburg, Salzburg, Austria
- 5 Department of Plastic and Reconstructive Surgery, Hospital of the Barmherzige Brüder, Paracelsus Medical University Salzburg, Salzburg, Austria
- 6 L'Oréal Research and Innovation, Aulnay-sous-Bois, France
Received: August 5, 2020 Accepted: July 17, 2021 Published: August 2, 2021https://doi.org/10.18632/aging.203385
How to Cite
Copyright: © 2021 Breunig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.