热门
Role for the endoplasmic reticulum stress sensor IRE1 alpha in liver regenerative responses
文献类型：期刊论文
| 作者 | Liu, Yang; Shao, Mengle; Wu, Ying; Yan, Cheng; Jiang, Shan; Liu, Jingnan; Dai, Jianli; Yang, Liu（杨柳）; Li, Jia; Jia, Weiping |
| 刊名 | JOURNAL OF HEPATOLOGY
 |
| 出版日期 | 2015 |
| 卷号 | 62期号:3页码:590-598 |
| 关键词 | Unfolded protein response IRE1 alpha Liver regeneration Hepatocyte proliferation STAT3 |
| 通讯作者 | Liu, Y (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China. |
| 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. |
| 类目[WOS] | Gastroenterology & Hepatology |
| 研究领域[WOS] | Gastroenterology & Hepatology |
| 关键词[WOS] | UNFOLDED PROTEIN RESPONSE ; PANCREATIC BETA-CELLS ; ER STRESS ; MESSENGER-RNA ; INTERLEUKIN-6-DEFICIENT MICE ; TRANSMEMBRANE PROTEIN ; CARBON-TETRACHLORIDE ; TRANSCRIPTION FACTOR ; PARTIAL-HEPATECTOMY ; THERAPEUTIC TARGET |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000349855400015 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/271]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 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：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。