Uncovering Novel Landscape and Functional MicroRNA-Targets for Androgenetic Alopecia

Androgenetic alopecia (AGA) is an inherited, androgen-driven disorder. The crucial role of microRNAs (miRNA) in hair follicle (HF) development is well known; however, a role for miRNAs in AGA pathophysiology at the molecular level remains largely unclear. Here, we integrate miRNA with previously reported mRNA sequencing profiles, and construct specific miRNA-mRNA regulatory networks in AGA. Based on this, considerable downregulated predicted target genes of AGA bulge-containing groups were related to structure modulation, outlining the potential role of microenvironment remodeling in hair follicle stem cells (HFSCs) dysfunction in AGA. Moreover, we have established an AGA model using organ-cultured balding AGA HFs (hair follicles in the leading edge of hair recession areas in the vertex of AGA patients) to explore the role of microRNA in AGA. Using this integrative method, combined with our molecular validation data, we preliminarily describe microRNAs potentially regulating various significant pathological processes of AGA (androgen signaling, hair cycle, inflammation) and present evidence that miR-146b-5p might be capable of promoting hair growth and improving the inflammatory microenvironment in AGA HFs, presenting a promising miRNA target for AGA treatment.