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

Mohammadi, P ; Sharif University of Technology | 2021

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  1. Type of Document: Article
  2. DOI: 10.1016/j.jdermsci.2020.11.002
  3. Publisher: Elsevier Ireland Ltd , 2021
  4. Abstract:
  5. 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. © 2020 Japanese Society for Investigative Dermatology
  6. Keywords:
  7. MicroRNA ; MicroRNA 324 3p ; Mitogen activated protein kinase ; Unclassified drug ; MIRN324 microRNA, human ; Protein kinase inhibitor ; TGFBR1 protein, human ; Transforming growth factor beta ; Androgenic alopecia ; Cell migration ; Cell selection ; Controlled study ; Enzyme regulation ; Gene control ; Gene expression ; Gene targeting ; Genetic marker ; Hair cell (inner ear) ; Hair follicle cell ; Human ; Human cell ; Human cell culture ; Human tissue ; Immunofluorescence assay ; Keratinocyte ; Molecular dynamics ; Organ culture ; Priority journal ; Real time reverse transcription polymerase chain reaction ; RNA analysis ; Stem cell ; TGF beta signaling ; Wound healing assay ; Cell motion ; Cytology ; Drug effect ; Gene expression profiling ; Genetics ; Growth, development and aging ; Hair follicle ; MAPK signaling ; Metabolism ; Middle aged ; Pathology ; Adult ; Alopecia ; Cell Differentiation ; Cell Line ; Cell Movement ; Cell Proliferation ; Humans ; Keratinocytes ; Male ; MAP Kinase Signaling System ; MicroRNAs ; Protein Kinase Inhibitors ; Receptor, Transforming Growth Factor-beta Type I ; Stem Cells
  8. Source: Journal of Dermatological Science ; Volume 101, Issue 1 , 2021 , Pages 49-57 ; 09231811 (ISSN)
  9. URL: https://linkinghub.elsevier.com/retrieve/pii/S0923181120303510