Defining microRNA signatures of hair follicular stem and progenitor cells in healthy and androgenic alopecia patients

Parvaneh Mohammadi, Mohammad Ali Nilforoushzadeh, Khalil Kass Youssef, Ali Sharifi-Zarchi, Sharif Moradi, Pardis Khosravani, Raheleh Aghdami, Payam Taheri, Ghasem Hosseini Salekdeh, Hossein Baharvand, Nasser Aghdami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The exact pathogenic mechanism causes hair miniaturization during androgenic alopecia (AGA) has not been delineated. Recent evidence has shown a role for non-coding regulatory RNAs, such as microRNAs (miRNAs), in skin and hair disease. There is no reported information about the role of miRNAs in hair epithelial cells of AGA. 

Objectives: To investigate the roles of miRNAs affecting AGA in normal and patient's epithelial hair cells. 

Methods: Normal follicular stem and progenitor cells, as well as follicular patient's stem cells, were sorted from hair follicles, and a miRNA q-PCR profiling to compare the expression of 748 miRNA (miRs) in sorted cells were performed. Further, we examined the putative functional implication of the most differentially regulated miRNA (miR-324-3p) in differentiation, proliferation and migration of cultured keratinocytes by qRT-PCR, immunofluorescence, and scratch assay. To explore the mechanisms underlying the effects of miR-324-3p, we used specific chemical inhibitors targeting pathways influenced by miR-324-3p. 

Result: We provide a comprehensive assessment of the “miRNome” of normal and AGA follicular stem and progenitor cells. Differentially regulated miRNA signatures highlight several miRNA candidates including miRNA-324-3p as mis regulated in patient's stem cells. We find that miR-324-3p promotes differentiation and migration of cultured keratinocytes likely through the regulation of mitogen-activated protein kinase (MAPK) and transforming growth factor (TGF)-β signaling. Importantly, pharmacological inhibition of the TGF-β signaling pathway using Alk5i promotes hair shaft elongation in an organ-culture system. 

Conclusion: Together, we offer a platform for understanding miRNA dynamic regulation in follicular stem and progenitor cells in baldness and highlight miR-324-3p as a promising target for its treatment.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalJournal of Dermatological Science
Volume101
Issue number1
DOIs
Publication statusPublished - Jan 2021
Externally publishedYes

Keywords

  • miRNA
  • Androgenic alopecia
  • Hair follicular stem cells
  • miR-324-3p

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