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Downregulation of circular RNA ETS1 promotes SLE activity and inhibits Treg cell differentiation through miR-1205/FoxP3 molecular axis.
Zou, Hongju; Ma, Sha; Li, Li; Xia, Xixi; Zhou, Yan; Zhang, Ruixian.
Afiliación
  • Zou H; Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China.
  • Ma S; Department of Rheumatology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China.
  • Li L; School of Public Health, Dali University, Dali, Yunnan 671013, China.
  • Xia X; Department of Laboratory Medicine, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China.
  • Zhou Y; Department of Nephrology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China. Electronic address: 2571566181@qq.com.
  • Zhang R; Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China. Electronic address: zhangrx2005@163.com.
Int Immunopharmacol ; 128: 111539, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38244519
ABSTRACT

PURPOSE:

This study aimed to explore the mechanism by which systemic lupus erythematosus (SLE) activity is promoted through Treg inhibition from the perspective of ceRNA.

METHODS:

qRT-PCR was used to detect the expressions of circETS1, miR-1205, and FoxP3 in clinical SLE patient samples. Overexpression of circETS1and miR-1205, along with knockdown of miR-1205 and FoxP3 were conducted in CD4+ T cells, while the proliferation of helper T cell 17 (Th17) and regulatory T cell (Treg) was detected. Arescue assay was performed to verify the molecular mechanism of circETS1/miR-1205/Foxp3 mRNA axis in regulating CD4+ T cell differentiation. In the in vivo experiment, the expression of miR-1205 in SLE mice was intervened, and renal function, inflammatory factors, and serum complement were measured. Additionally, Treg/Th17 cell ratio was detected by flow cytometry.

RESULTS:

In SLE patients, Treg cells were found to decrease, while Th17 cells increased. Transfection with circETS1 overexpression led to CD4+ T cells differentiating into Treg cells, causing an imbalance in the Th17/Treg ratio. Transfection of miR-1205 mimic and si-FoxP3 could reverse the effect of circETS1 overexpression. Moreover, inhibiting the expression of miR-1205 showed therapeutic effects on SLE mice.

CONCLUSION:

circETS1 inhibits Treg via the miR-1205/FoxP3 axis, thereby promoting SLE activity, which may become a new target for SLE treatment.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: MicroARNs / Lupus Eritematoso Sistémico Límite: Animals / Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Asunto principal: MicroARNs / Lupus Eritematoso Sistémico Límite: Animals / Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China