Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN
Abstract The liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat die...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03514-0 |
| _version_ | 1818437558829318144 |
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| author | Mi Tian Jingjing Wang Shangming Liu Xinyun Li Jingyuan Li Jianmin Yang Cheng Zhang Wencheng Zhang |
| author_facet | Mi Tian Jingjing Wang Shangming Liu Xinyun Li Jingyuan Li Jianmin Yang Cheng Zhang Wencheng Zhang |
| author_sort | Mi Tian |
| collection | DOAJ |
| description | Abstract The liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuRLKO) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3′ untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuRLKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN. |
| first_indexed | 2024-12-14T17:26:35Z |
| format | Article |
| id | doaj.art-fc4ede5867d74f1d9b4ceeddef593eb4 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-14T17:26:35Z |
| publishDate | 2021-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-fc4ede5867d74f1d9b4ceeddef593eb42022-12-21T22:53:13ZengNature Publishing GroupCell Death and Disease2041-48892021-03-0112311210.1038/s41419-021-03514-0Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTENMi Tian0Jingjing Wang1Shangming Liu2Xinyun Li3Jingyuan Li4Jianmin Yang5Cheng Zhang6Wencheng Zhang7The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Physiology & Pathophysiology, School of Basic Medical Sciences, Shandong UniversityDepartment of Histology and Embryology, School of Basic Medical Sciences, Shandong UniversityThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract The liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuRLKO) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3′ untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuRLKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.https://doi.org/10.1038/s41419-021-03514-0 |
| spellingShingle | Mi Tian Jingjing Wang Shangming Liu Xinyun Li Jingyuan Li Jianmin Yang Cheng Zhang Wencheng Zhang Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN Cell Death and Disease |
| title | Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN |
| title_full | Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN |
| title_fullStr | Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN |
| title_full_unstemmed | Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN |
| title_short | Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN |
| title_sort | hepatic hur protects against the pathogenesis of non alcoholic fatty liver disease by targeting pten |
| url | https://doi.org/10.1038/s41419-021-03514-0 |
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