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Role for the endoplasmic reticulum stress sensor IRE1 alpha in liver regenerative responses

文献类型：期刊论文

作者Liu, Yang2; Shao, Mengle2; Wu, Ying2; Yan, Cheng; Jiang, Shan2,3; Liu, Jingnan; Dai, Jianli4; Yang, Liu2; Li, Jia5; Jia, Weiping3
刊名JOURNAL OF HEPATOLOGY
出版日期2015-03
卷号62期号:3页码:590-598
关键词Unfolded protein response IRE1 alpha Liver regeneration Hepatocyte proliferation STAT3
ISSN号0168-8278
DOI10.1016/j.jhep.2014.10.022
文献子类Article
英文摘要Background & Aims: As the main detoxifying organ of the body, the liver possesses a remarkable ability to regenerate after toxic injury, tissue resection or viral infection. A growing number of cellular signaling pathways have been implicated in orchestrating the process of liver regeneration. Here we investigated the role of inositol-requiring enzyme-1 alpha (IRE1 alpha), a key signal transducer of the unfolded protein response (UPR), in liver regeneration. Methods: Using mice with hepatocyte-specific deletion of IRE1 alpha, we examined the role of IRE1 alpha in liver regeneration after challenges with carbon tetrachloride (CCl4) or hepatic surgery. We also investigated if IRE1 alpha deficiency could affect the activation state of signal transducer and activator of transcription 3 (STAT3) in hepatocytes. Using co-immunoprecipitation and glutathione S-transferase (GST) pull-down assays, we analyzed whether IRE1 alpha could interact with STAT3 to regulate its phosphorylation. Results: We found that in response to CCl4-induced liver damage or after two-thirds partial hepatectomy (PH), abrogation of IRE1 alpha caused marked exacerbation of liver injury and impairment in regenerative proliferation of hepatocytes in mice. Furthermore, IRE1a deficiency resulted in dampened STAT3 activation, and restoration of IRE1 alpha expression led to sustained phosphorylation of STAT3 in IRE1 alpha-null hepatocytes. Additionally, IRE1 alpha could directly and constitutively associate with STAT3, leading to elevated phosphorylation when stimulated by IL-6. Conclusions: These results suggest that IRE1 alpha may promote liver regeneration through acting as a signaling platform to regulate the STAT3 pathway. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
WOS关键词UNFOLDED PROTEIN RESPONSE ; PANCREATIC BETA-CELLS ; ER STRESS ; MESSENGER-RNA ; INTERLEUKIN-6-DEFICIENT MICE ; TRANSMEMBRANE PROTEIN ; CARBON-TETRACHLORIDE ; TRANSCRIPTION FACTOR ; PARTIAL-HEPATECTOMY ; THERAPEUTIC TARGET
资助项目Ministry of Science and Technology[00000000] ; National Natural Science Foundation of China[2012CB524900] ; National Natural Science Foundation of China[81420108006] ; National Natural Science Foundation of China[31230036] ; National Natural Science Foundation of China[81321062] ; National Natural Science Foundation of China[91213306] ; National Natural Science Foundation of China[2011CB910900]
WOS研究方向Gastroenterology & Hepatology
语种英语
WOS记录号WOS:000349855400015
出版者ELSEVIER SCIENCE BV
源URL[http://119.78.100.183/handle/2S10ELR8/276630]  
专题国家新药筛选中心
药物安全性评价中心
通讯作者Liu, Yong
作者单位1.Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
2.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China;
3.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab,Shanghai Clin Ctr Diabet, Shanghai Diabet Inst,Shanghai Key Lab Diabet Mell, Shanghai 200233, Peoples R China;
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Liu, Yang,Shao, Mengle,Wu, Ying,et al. Role for the endoplasmic reticulum stress sensor IRE1 alpha in liver regenerative responses[J]. JOURNAL OF HEPATOLOGY,2015,62(3):590-598.
APA Liu, Yang.,Shao, Mengle.,Wu, Ying.,Yan, Cheng.,Jiang, Shan.,...&Liu, Yong.(2015).Role for the endoplasmic reticulum stress sensor IRE1 alpha in liver regenerative responses.JOURNAL OF HEPATOLOGY,62(3),590-598.
MLA Liu, Yang,et al."Role for the endoplasmic reticulum stress sensor IRE1 alpha in liver regenerative responses".JOURNAL OF HEPATOLOGY 62.3(2015):590-598.

入库方式： OAI收割

来源：上海药物研究所

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