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

Abstract

BackgroundThe 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 hypoxiainducible factor (HIF)-1, Wnt/β-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/βcatenin 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 in AGA.What is already known about this topic?• Multiple differentially expressed genes and signalling pathways have been found between hair follicles (HFs) in the balding area (frontal and vertex regions) and nonbalding area (occipital region) of individuals with androgenetic alopecia (AGA). • A whole-transcriptome atlas of the vertex and occipital region is lacking.

Mechanical epilation exerts complex biological effects on human hair follicles and perifollicular skin: An ex vivo study approach

“…Hence, our findings regarding sebocyte apoptosis, IP collapse, local inflammation, and pain-related pathways require confirmation in additional donors and subsequent studies. Finally, the range of biomarkers studied should be greatly expanded, including wound healing/trauma-associated products of genes that have recently been reported to be associated with androgenetic alopecia [169] or that are known to regulate wounding-induced HF neogenesis in adult mice [170]; moreover, indicators of long-term HF and skin wounding memory [171], especially after repetitive epilation, could be studied. In addition, the impact of epilation on human HF innervation [172], neuroendocrine signalling [173][174][175], and the human HF microbiome [165,176] remains to be investigated, and our hypothesis-driven protein−/celllevel data should be complemented with hypothesis-free transcriptomic data at various time points post-epilation.…”

Evaluation of short-term hair follicle storage conditions for maintenance of RNA integrity

“…While lower numbers of hair follicles were used per sample, it is unclear whether this, the storage conditions or the extraction protocol was the reason for the poorer quality of RNA reported. Many such studies aim to evaluate gene expression to better understand hair growth in order to provide potential targets for the treatment of human hair loss and other skin conditions (23,24). An equine study by Naboulsi et al, (2022), found that keratin-related genes were more plentiful in hair follicle samples than in skin biopsies, making HF an excellent tissue for functional studies on colouration, shape, and growth of hair as these characteristics can be attenuated in skin biopsies.…”

The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia

“…Assays using HFs obtained through plucking, follicular unit extraction (FUE), and skin biopsies have been performed. Through a comprehensive literature search, we found 9 studies involving human HGs [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. In most studies (67%), the complete HF was used to obtain mRNA samples.…”