1. The life in a gradient: calcium, the lncRNA SPRR2C and mir542/mir196a meet in the epidermis to regulate the aging process
- Author
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Fritz Aberger, Claudia Neuhofer, Maria Karolin Streubel, Elisabeth Russe, Katharina Kobler, Sven Breunig, Veronika Wallner, Klaus Richter, Albert Duranton, Michael Breitenbach, Wolfgang Gruber, Peter Steinbacher, Jutta Duschl, Gottfried Wechselberger, Mark Rinnerthaler, Johannes Bischof, and Herbert Wimmer
- Subjects
Keratinocytes ,Aging ,Cell division ,Stratum granulosum ,pseudogene ,chemistry.chemical_element ,Gene Expression ,Calcium ,Cornified envelope ,lncRNA ,Cornified Envelope Proline-Rich Proteins ,medicine ,Humans ,Progenitor cell ,Cell Proliferation ,miRNA ,Corneocyte ,integumentary system ,epidermal barrier ,Cell Differentiation ,Cell Biology ,Cell biology ,Skin Aging ,body regions ,MicroRNAs ,medicine.anatomical_structure ,chemistry ,Epidermal Cells ,embryonic structures ,RNA, Long Noncoding ,Epidermis ,Stratum basale ,Research Paper - 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.
- Published
- 2020