GADD45 beta stabilized by direct interaction with HSP72 ameliorates insulin resistance and lipid accumulation | |
Dong, Yunxia1,2; Ma, Ningning1,2,3; Fan, Lei1,2; Yuan, Luyang4; Wu, Qian1; Gong, Likun1,2; Tao, Zhouteng1; Chen, Jing1,2; Ren, Jin1,2 | |
刊名 | PHARMACOLOGICAL RESEARCH |
2021-11-01 | |
卷号 | 173页码:11 |
关键词 | Non-alcoholic fatty liver disease GADD45 beta HSP72 Lipid accumulation Insulin resistance |
ISSN号 | 1043-6618 |
DOI | 10.1016/j.phrs.2021.105879 |
通讯作者 | Tao, Zhouteng(taozhouteng@simm.ac.cn) ; Chen, Jing(jingchen@simm.ac.cn) ; Ren, Jin(jren@cdser.simm.ac.cn) |
英文摘要 | 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. |
资助项目 | National Natural Science Foundation of China[81870401] |
WOS关键词 | FATTY LIVER-DISEASE ; GENE-EXPRESSION ; OXIDATIVE STRESS ; PROTECTS ; TRANSDUCTION ; DEGRADATION ; SIGNATURES ; PATHWAY ; MATRINE ; MICE |
WOS研究方向 | Pharmacology & Pharmacy |
语种 | 英语 |
出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
WOS记录号 | WOS:000704159400021 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/298799] |
专题 | 中国科学院上海药物研究所 |
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 |
推荐引用方式 GB/T 7714 | 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,2021,173:11. |
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,173,11. |
MLA | Dong, Yunxia,et al."GADD45 beta stabilized by direct interaction with HSP72 ameliorates insulin resistance and lipid accumulation".PHARMACOLOGICAL RESEARCH 173(2021):11. |
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