Research Paper Volume 9, Issue 11 pp 2376—2396

An expression screen for aged-dependent microRNAs identifies miR-30a as a key regulator of aging features in human epidermis

Charlotte Muther 1, , Lara Jobeili 3, , Maëlle Garion 1, , Sandrine Heraud 2, , Amélie Thepot 2, , Odile Damour 3, , Jérôme Lamartine 1, ,

  • 1 Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, University Claude Bernard Lyon I, F69367 Lyon, France
  • 2 LabSkin Creations, F69003 Lyon, France
  • 3 Banque de Tissus et Cellules, Hospices Civiles de Lyon, F69003 Lyon, France

received: July 7, 2017 ; accepted: November 11, 2017 ; published: November 19, 2017 ;

https://doi.org/10.18632/aging.101326
How to Cite

Copyright: Muther 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.

Abstract

The mechanisms affecting epidermal homeostasis during aging remain poorly understood. To identify age-related microRNAs, a class of non-coding RNAs known to play a key role in the regulation of epidermal homeostasis, an exhaustive miRNA expression screen was performed in human keratinocytes from young or elderly subjects. Many microRNAs modulated by aging were identified, including miR-30a, in which both strands were overexpressed in aged cells and epidermal tissue. Stable MiR-30a over-expression strongly impaired epidermal differentiation, inducing severe barrier function defects in an organotypic culture model. A significant increase was also observed in the level of apoptotic cells in epidermis over-expressing miR-30a. Several gene targets of miR-30a were identified in keratinocytes, including LOX (encoding lysyl oxidase, a regulator of the proliferation/differentiation balance of keratinocytes), IDH1 (encoding isocitrate dehydrogenase, an enzyme of cellular metabolism) and AVEN (encoding a caspase inhibitor). Direct regulation of LOX, IDH1 and AVEN by miR-30a was confirmed in human keratinocytes. They were, moreover, observed to be repressed in aged skin, suggesting a possible link between miR-30a induction and skin-aging phenotype. This study revealed a new miRNA actor and deciphered new molecular mechanisms to explain certain alterations observed in epidermis during aging and especially those concerning keratinocyte differentiation and apoptosis.

Abbreviations

UV (Ultra Violet): QPCR (Quantitative Polymerase Chain Reaction), SE (Skin Equivalent), RE (Reconstructed epidermis), HES (Hematoxylin Eosin Saffron), MRE (MicroRNA Responding Element), TEWL (Trans-Epidermal Water Loss), MOI (Multiplicity Of Infection), SD (Standard Deviation), HPK (Human Primary Keratinocytes).