miR‑146a‑5p protects against renal injury in MRL/lpr mice via improvement of the Treg/Th17 imbalance by targeting the TRAF6/NF‑κB axis

Teng,Jiajia; Yang,Feng; Li,Xiaoling

doi:10.3892/etm.2022.11720

miR‑146a‑5p protects against renal injury in MRL/lpr mice via improvement of the Treg/Th17 imbalance by targeting the TRAF6/NF‑κB axis

Authors:
- Jiajia Teng
- Feng Yang
- Xiaoling Li
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Affiliations: Department of Nephropathy, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264001, P.R. China, Department of Rheumatology, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264001, P.R. China
Published online on: November 22, 2022 https://doi.org/10.3892/etm.2022.11720
Article Number: 21
Copyright: © Teng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dysregulated microRNA (miRNA or miR) expression is an important cause of immune homeostasis disorder in patients with systemic lupus erythematosus and lupus nephritis (LN). The present study evaluated the possibility of using miR‑146a‑5p as a therapeutic target for treating LN. The effects of miR‑146a‑5p on lupus syndrome in MRL/lpr mice were evaluated. MRL/lpr mice were injected with miR‑146a‑5p agomir (M146AG) or agomir negative control (NC). Renal function index, pathology and protein expression levels of inflammatory factors in MRL/lpr mice were evaluated after M146AG or agomir NC treatment. Reverse transcription‑quantitative PCR, western blotting and immunofluorescence were used to assess the effect of M146AG on mRNA and protein expression levels of (tumor necrosis factor receptor‑associated factor 6) TRAF6/NF‑κB axis components. A luciferase dual reporter system was used to assess the mechanism of regulation of TRAF6/NF‑κB axis expression. Finally, flow cytometry was used to assess the regulatory effect of M146AG on regulatory T cell (Treg)/T helper 17 (Th17) balance. The findings demonstrated that M146AG ameliorated renal lesions and the inflammatory response in MRL/lpr mice. TRAF6 was demonstrated to be targeted and significantly negatively regulated by miR‑146a‑5p. M146AG intervention significantly increased expression of miR‑146a‑5p and significantly downregulated the mRNA and protein expression levels of TRAF6 and NF‑κB in CD4⁺ T cells of MRL/lpr mice. Furthermore, M146AG intervention alleviated Treg/Th17 imbalance in MRL/lpr mice peripheral blood. The present findings demonstrated that M146AG improved Treg/Th17 imbalance and alleviated renal lesions in MRL/lpr mice by targeting the TRAF6/NF‑κB axis. This may provide a new theoretical basis for the clinical diagnosis and treatment of LN.

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