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Research Paper|Volume 12, Issue 13|pp 12726—12739

EZH2-mediated inhibition of microRNA-22 promotes differentiation of hair follicle stem cells by elevating STK40 expression

Bingjie Cai1, Min Li2, Yunpeng Zheng1, Yakun Yin1, Fangcao Jin1, Xuyang Li1, Juan Dong1, Xiaoyan Jiao1, Xiaojun Liu3, Kun Zhang4, Dongqin Li1, Junmin Wang5, Guangwen Yin1
  • 1Department of Dermatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China
  • 2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou 450003, P. R. China
  • 3,, Henan Province Medical Instrument Testing Institute, Zhengzhou 450018, P.R. China
  • 4School of Life Sciences, Zhengzhou University, Zhengzhou 450001, P.R. China
  • 5Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, P.R. China
Received: January 7, 2020Accepted: March 31, 2020Published: July 12, 2020
https://doi.org/10.18632/aging.103165

Copyright © 2020 Cai 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

Hair follicle stem cells (HFSCs) contribute to the regeneration of hair follicles (HFs), thus accelerating hair growth. microRNAs (miRs) are potential regulators in various cellular processes, including HFSC proliferation and differentiation. This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40 (STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. Gain- and loss-of-function approaches were adopted to explore the roles of EZH2, miR-22, and STK40 in the proliferation and apoptosis of HFSCs, along with the functional relevance of MEF2-ALP activity. STK40 was elevated during HFSC differentiation, which was found to facilitate HFSC proliferation, but impede their apoptosis by activating MEF2-ALP. Mechanically, miR-22 targeted and inversely regulated STK40, which inhibited MEF2-ALP activity to impede HFSC proliferation and differentiation. Moreover, EZH2 elevated the STK40 expression by repressing miR-22 to promote the proliferation and differentiation of HFSCs. Furthermore, in vivo experiments further validated the roles of EZH2 and STK40 on hair follicle neogenesis and hair growth. Collectively, EZH2 elevated the STK40 expression by downregulating miR-22, consequently accelerating differentiation of HFSCs and hair growth, which sheds light on the underlying molecular mechanism responsible for hair growth.