Insights into male androgenetic alopecia using comparative transcriptome profiling: hypoxia-inducible factor-1 and Wnt/β-catenin signalling pathways

作者：Qingmei Liu, Yulong Tang, Yan Huang, Jian Wang, Kai Yang, Yuting Zhang, Weilin Pu, Jing Liu, Xiangguang Shi, Yanyun Ma, Chunya Ni, Yue Zhang, Yifei Zhu, Haiyang Li, Jiucun Wang, Jinran Lin, Wenyu Wu · 发表于：British Journal of Dermatology · 年份：2022 · DOI：10.1111/bjd.21783 · 被引用次数：55 · 研究领域：Hair Growth and Disorders、Facial Rejuvenation and Surgery Techniques、Skin and Cellular Biology Research

BACKGROUND: The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region. OBJECTIVES: To identify biological differences among HF subpopulations. METHODS: Paired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay. Furthermore, HF and cell experiments were conducted on the identified key genes to reveal their roles in AGA. RESULTS: Transcriptome profiles revealed that 506 mRNAs, 55 microRNAs and 127 long noncoding RNAs were differentially expressed in the AGA vertex HFs. Pathway analysis of mRNAs and microRNAs revealed involvement of the hypoxia-inducible factor (HIF)-1, Wnt/β-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/β-catenin pathway inhibitors (SERPINF1, SFRP2) was experimentally validated. In vitro studies revealed that reduction of EGLN1, EGLN3, SERPINF1 and SFRP2 stimulated proliferation of dermal papilla cells. Ex vivo HF studies showed that downregulation of EGLN1, EGLN3 and SERPINF1 promoted HF growth, postponed HF catagen transition, and prolonged the anagen stage, suggesting that these genes may be potentially utilized as therapeutic targets for AGA. CONCLUSIONS: We characterized key transcriptome changes in male AGA HFs, and found that HIF-1 pathway-related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (SERPINF1, SFRP2) may play important roles...