Defining microRNA signatures of hair follicular stem and progenitor cells in healthy and androgenic alopecia patients.
Adult
Alopecia
/ genetics
Cell Differentiation
/ drug effects
Cell Line
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Gene Expression Profiling
Hair Follicle
/ cytology
Humans
Keratinocytes
MAP Kinase Signaling System
/ drug effects
Male
MicroRNAs
/ metabolism
Middle Aged
Protein Kinase Inhibitors
/ pharmacology
Receptor, Transforming Growth Factor-beta Type I
/ antagonists & inhibitors
Stem Cells
/ metabolism
Transforming Growth Factor beta
/ metabolism
Androgenic alopecia
Hair follicular stem cells
miR-324-3p
miRNA
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
30
04
2020
revised:
22
10
2020
accepted:
03
11
2020
pubmed:
14
11
2020
medline:
29
6
2021
entrez:
13
11
2020
Statut:
ppublish
Résumé
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. To investigate the roles of miRNAs affecting AGA in normal and patient's epithelial hair cells. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
To investigate the roles of miRNAs affecting AGA in normal and patient's epithelial hair cells.
METHODS
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
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 33183906
pii: S0923-1811(20)30351-0
doi: 10.1016/j.jdermsci.2020.11.002
pii:
doi:
Substances chimiques
MIRN324 microRNA, human
0
MicroRNAs
0
Protein Kinase Inhibitors
0
Transforming Growth Factor beta
0
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
TGFBR1 protein, human
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
49-57Informations de copyright
Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.