Defining microRNA signatures of hair follicular stem and progenitor cells in healthy and androgenic alopecia patients
Por:
Mohammadi, P, Nilforoushzadeh, M, Youssef, K, Sharifi-Zarchi, A, Moradi, S, Khosravani, P, Aghdami, R, Taheri, P, Salekdeh, G, Baharvand, H and Aghdami, N
Publicada:
1 ene 2021
Ahead of Print:
1 ene 2021
Resumen:
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)-beta signaling. Importantly, pharmacological inhibition of the TGF-beta 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. (C) 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
Filiaciones:
Mohammadi, P:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
Univ Sci & Culture, Dept Dev Biol, Tehran, Iran
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, Tehran, Iran
Nilforoushzadeh, M:
Univ Tehran Med Sci, Skin & Stem Cell Res Ctr, Tehran, Iran
:
Inst Neurociencias CSIC UMH, Sant Joan dAlacant, Spain
Sharifi-Zarchi, A:
Sharif Univ Technol, Comp Engn Dept, Tehran, Iran
Moradi, S:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
Khosravani, P:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
Aghdami, R:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, Tehran, Iran
Taheri, P:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
Salekdeh, G:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
Baharvand, H:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Stem Cells & Dev Biol, Tehran, Iran
Univ Sci & Culture, Dept Dev Biol, Tehran, Iran
Aghdami, N:
ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, Tehran, Iran
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