PPARγ attenuates hepatic inflammation and oxidative stress of non‑alcoholic steatohepatitis via modulating the miR‑21‑5p/SFRP5 pathway

Zhang,Xiying; Deng,Fang; Zhang,Yuping; Zhang,Xiaohong; Chen,Jianfei; Jiang,Youzhao

doi:10.3892/mmr.2021.12463

PPARγ attenuates hepatic inflammation and oxidative stress of non‑alcoholic steatohepatitis via modulating the miR‑21‑5p/SFRP5 pathway

Authors:
- Xiying Zhang
- Fang Deng
- Yuping Zhang
- Xiaohong Zhang
- Jianfei Chen
- Youzhao Jiang
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Affiliations: Department of Endocrinology, Banan People's Hospital of Chongqing, Chongqing 401320, P.R. China, Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing 400038, P.R. China, Department of Cardiology, Banan People's Hospital of Chongqing, Chongqing 401320, P.R. China
Published online on: September 24, 2021 https://doi.org/10.3892/mmr.2021.12463
Article Number: 823
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inflammation and oxidative stress are key steps in the progression of non‑alcoholic steatohepatitis (NASH). Intervention in these two processes will therefore benefit NASH treatment. Peroxisome proliferator‑activated receptor γ (PPARγ), as a multiple functional transcription factor, has been reported to be involved in the prevention of NASH progression. However, the mechanism by which PPARγ prevents NASH remains to be elucidated. The present study demonstrated that the level of PPARγ was inversely correlated with that of microRNA (miRNA/miRs)‑21‑5p in both mice and humans with NASH. Activation of PPARγ inhibited lipid droplet accumulation, hepatic inflammation and oxidative stress by downregulating miR‑21‑5p in an in vitro model. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that PPARγ suppressed transcriptional activity of miR‑21‑5p and bound to miR‑21‑5p promoter region. Furthermore, PPARγ downregulated miR‑21‑5p while miR‑21‑5p upregulated secreted frizzled‑related protein 5 (SFRP5) by targeting the 3'‑UTR of its mRNA. In vivo experiments revealed that PPARγ repressed inflammation and oxidative stress and miR‑21‑5p expression while increased SFRP5 level in a NASH mouse model. In summary, PPARγ attenuates inflammation and oxidative stress in NASH by modulating the miR‑21‑5p/SFRP5 pathway, thus holding promise of a new target for NASH treatment.

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