GADD45 beta stabilized by direct interaction with HSP72 ameliorates insulin resistance and lipid accumulation
2021-11
发表期刊PHARMACOLOGICAL RESEARCH (IF:9.1[JCR-2023],9.0[5-Year])
ISSN1043-6618
EISSN1096-1186
卷号173
DOI10.1016/j.phrs.2021.105879
摘要Growth arrest and DNA damage-inducible 45 beta (GADD45 beta) belongs to the GADD45 family which is small acidic proteins in response to cellular stress. GADD45 beta has already been reported to have excellent capabilities against cancer, innate immunity and neurological diseases. However, there is little information regard GADD45 beta and non-alcoholic fatty liver disease (NAFLD). In the current work, we found that the expression of GADD45 beta was markedly decreased in the livers of NAFLD patients via analyzing Gene Expression Omnibus (GEO) dataset and in mouse model through detecting its mRNA in high-fat-high-fructose diet (HFHFr)-fed mice. Moreover, the results from in vivo experiment demonstrated that overexpression of GADD45 beta by AAV8-mediated gene transfer in HFHFr-fed mouse model could reduce the level of serum and hepatic triglyceride (TG), and alleviate insulin resistance. Subsequently, by combining immunoprecipitation (IP) and mass spectrometry, we identified that HSP72 directly interacted with GADD45 beta to prevent GADD45 beta from being degraded by the proteasome pathway. Finally, the benefits of GADD45 beta in regulating key factors of TG synthesis and insulin signaling pathway were abolished after HSP72 knockdown. In conclusion, GADD45 beta stabilized by the interaction with HSP72 could alleviate the NAFLD-related pathologies, suggested it might be a potential target for the treatment of NAFLD.
关键词Non-alcoholic fatty liver disease GADD45 beta HSP72 Lipid accumulation Insulin resistance
收录类别SCIE
语种英语
WOS研究方向Pharmacology & Pharmacy
WOS类目Pharmacology & Pharmacy
WOS记录号WOS:000704159400021
出版者ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128571
专题生命科学与技术学院_博士生
通讯作者Tao, Zhouteng; Chen, Jing; Ren, Jin
作者单位
1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Safety Evaluat & Res, 501 Haike Rd, Shanghai 201203, Peoples R China;
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;
3.Shanghai Tech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China;
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China
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Dong, Yunxia,Ma, Ningning,Fan, Lei,et al. GADD45 beta stabilized by direct interaction with HSP72 ameliorates insulin resistance and lipid accumulation[J]. PHARMACOLOGICAL RESEARCH,2021,173.
APA Dong, Yunxia.,Ma, Ningning.,Fan, Lei.,Yuan, Luyang.,Wu, Qian.,...&Ren, Jin.(2021).GADD45 beta stabilized by direct interaction with HSP72 ameliorates insulin resistance and lipid accumulation.PHARMACOLOGICAL RESEARCH,173.
MLA Dong, Yunxia,et al."GADD45 beta stabilized by direct interaction with HSP72 ameliorates insulin resistance and lipid accumulation".PHARMACOLOGICAL RESEARCH 173(2021).
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