|
KMID : 0032220230350010046
|
|
Annals of Dermatology
2023 Volume.35 No. 1 p.46 ~ p.55
|
|
|
MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata
|
|
Qi Si si
Sheng You yu
Hu Rui ming
Zhao Jun
Yang Qin ping
|
|
|
Abstract
|
|
|
Background : We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals.
Objective : To explore the role and mechanism of miR-1246 in severe AA.
Methods : Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA was used to measure cytokine levels.
Results : miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+IL-17+ cells proportion and the IL-17F level.
Conclusion : miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.
|
|
|
KEYWORD
|
|
|
Alopecia areata, MicroRNAs, Phosphorylation, Th17 cells, Transcription factors
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|
|