Yan, Kexiang; Zhang, Fuxin; Ren, Jie; Huang, Qiong; Yawalkar, Nikhil; Han, Ling (2023). MicroRNA-125a-5p regulates the effect of Tregs on Th1 and Th17 through targeting ETS-1/STAT3 in psoriasis. Journal of translational medicine, 21(1), p. 678. BioMed Central 10.1186/s12967-023-04427-6
|
Text
s12967-023-04427-6.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
BACKGROUND
Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear.
METHODS
The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo.
RESULTS
miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells.
CONCLUSIONS
miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.
Item Type: |
Journal Article (Original Article) |
---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology |
UniBE Contributor: |
Yawalkar, Nikhil |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1479-5876 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
02 Oct 2023 14:50 |
Last Modified: |
29 Oct 2023 02:25 |
Publisher DOI: |
10.1186/s12967-023-04427-6 |
PubMed ID: |
37773129 |
Uncontrolled Keywords: |
ETS-1 Psoriasis STAT3 Th17 Tregs miR125a-5p |
BORIS DOI: |
10.48350/186824 |
URI: |
https://boris.unibe.ch/id/eprint/186824 |