ARID2 Mitigates Hepatic Steatosis Via Promoting the Ubiquitination of JAK2

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2022 Nov 17

PMID 36396719

Authors

Hui-Jun Cao

Hao Jiang

Kai Ding

Xiao-Song Qiu

Ning Ma

Feng-Kun Zhang

Yi-Kang Wang

Qian-Wen Zheng

Ji Xia

Qian-Zhi Ni

Sheng Xu

Bing Zhu

Xu-Fen Ding

Tian-Wei Chen

Lin Qiu

Wei Chen

Zhi-Gang Li

Bin Zhou

Wen-Ming Feng

Dong Xie

Jing-Jing Li

Affiliations

Soon will be listed here.

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem. However, the complicated pathogenesis of NAFLD contributes to the deficiency of effective clinical treatment. Here, we demonstrated that liver-specific loss of Arid2 induced hepatic steatosis and this progression could be exacerbated by HFD. Mechanistic study revealed that ARID2 repressed JAK2-STAT5-PPARγ signaling pathway by promoting the ubiquitination of JAK2, which was mediated by NEDD4L, a novel E3 ligase for JAK2. ChIP assay revealed that ARID2 recruited CARM1 to increase H3R17me2a level at the NEDD4L promoter and activated the transcription of NEDD4L. Moreover, inhibition of Jak2 by Fedratinib in liver-specific Arid2 knockout mice alleviated HFD-induced hepatic steatosis. Downregulation of ARID2 and the reverse correlation between ARID2 and JAK2 were also observed in clinical samples. Therefore, our study has revealed an important role of ARID2 in the development of NAFLD and provided a potential therapeutic strategy for NAFLD.

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