Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice
Yanan Xu,1,* Zihao Li,1,* Shounan Lu,2 Chaoqun Wang,2 Shanjia Ke,2 Xinglong Li,2 Bing Yin,2 Hongjun Yu,2 Menghua Zhou,1 Shangha Pan,3 Hongchi Jiang,1 Yong Ma2 1Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Surgery, The First Affiliated Hospital...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-09-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/integrative-analysis-of-the-roles-of-lncrnas-and-mrnas-in-itaconate-me-peer-reviewed-fulltext-article-JIR |
| _version_ | 1818432670230642688 |
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| author | Xu Y Li Z Lu S Wang C Ke S Li X Yin B Yu H Zhou M Pan S Jiang H Ma Y |
| author_facet | Xu Y Li Z Lu S Wang C Ke S Li X Yin B Yu H Zhou M Pan S Jiang H Ma Y |
| author_sort | Xu Y |
| collection | DOAJ |
| description | Yanan Xu,1,* Zihao Li,1,* Shounan Lu,2 Chaoqun Wang,2 Shanjia Ke,2 Xinglong Li,2 Bing Yin,2 Hongjun Yu,2 Menghua Zhou,1 Shangha Pan,3 Hongchi Jiang,1 Yong Ma2 1Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongchi Jiang; Yong MaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, People’s Republic of ChinaTel +86-451-85553886; +86-451-85555376Email jianghc2013@163.com; mayong@ems.hrbmu.edu.cnPurpose: Itaconate is well known for its strong anti-inflammatory and antioxidant effect, but little is known about the potential role of long non-coding RNAs (lncRNAs) in the underlying mechanisms of hepatic ischemia-reperfusion (IR) injury. The aim of our study is to identify lncRNAs related to IR injury and itaconate-mediated protection and to demonstrate the mechanism by which itaconate acts in liver IR injury from the new perspective of lncRNAs.Methods: 4-Octyl itaconate (OI), a membrane-permeable derivative of itaconate, was used as a substitute for itaconate in our study. By using a mouse model of hepatic IR injury, serum and liver samples were collected to measure indexes of liver injury. Then, the liver samples of the mice were subjected to RNA sequencing (RNA-seq) and subsequent bioinformatics analysis.Results: Itaconate attenuated liver IR injury. A total of 138 lncRNAs and 156 messenger RNAs (mRNAs) were markedly differentially expressed in the IR-damaged liver tissues pretreated with OI compared with the matched liver tissues treated with vehicle. Functional analysis indicated that lncRNAs may indirectly participate in the effects of itaconate. Furthermore, 41 mRNAs were examined for the protein–protein interaction (PPI) network analysis, and a key gene cluster was defined. Then, combined the coexpression analysis and the cis and trans regulatory function prediction of lncRNAs, some “candidate” lncRNA-mRNA pairs which might relate to itaconate-mediated liver protection were identified, while the relationship requires future validation.Conclusion: Our study revealed that itaconate could protect the liver against IR injury and that lncRNAs might play a role in this process. Our study provides a novel way to investigate the mechanism by which itaconate affects hepatic IR injury and exerts its anti-inflammatory and antioxidative stress effects.Keywords: itaconate, ischemia-reperfusion injury, liver, lncRNA |
| first_indexed | 2024-12-14T16:08:53Z |
| format | Article |
| id | doaj.art-883c5bf725134e128adf2b60416a5572 |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-12-14T16:08:53Z |
| publishDate | 2021-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-883c5bf725134e128adf2b60416a55722022-12-21T22:55:03ZengDove Medical PressJournal of Inflammation Research1178-70312021-09-01Volume 144519453668639Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in MiceXu YLi ZLu SWang CKe SLi XYin BYu HZhou MPan SJiang HMa YYanan Xu,1,* Zihao Li,1,* Shounan Lu,2 Chaoqun Wang,2 Shanjia Ke,2 Xinglong Li,2 Bing Yin,2 Hongjun Yu,2 Menghua Zhou,1 Shangha Pan,3 Hongchi Jiang,1 Yong Ma2 1Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongchi Jiang; Yong MaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, People’s Republic of ChinaTel +86-451-85553886; +86-451-85555376Email jianghc2013@163.com; mayong@ems.hrbmu.edu.cnPurpose: Itaconate is well known for its strong anti-inflammatory and antioxidant effect, but little is known about the potential role of long non-coding RNAs (lncRNAs) in the underlying mechanisms of hepatic ischemia-reperfusion (IR) injury. The aim of our study is to identify lncRNAs related to IR injury and itaconate-mediated protection and to demonstrate the mechanism by which itaconate acts in liver IR injury from the new perspective of lncRNAs.Methods: 4-Octyl itaconate (OI), a membrane-permeable derivative of itaconate, was used as a substitute for itaconate in our study. By using a mouse model of hepatic IR injury, serum and liver samples were collected to measure indexes of liver injury. Then, the liver samples of the mice were subjected to RNA sequencing (RNA-seq) and subsequent bioinformatics analysis.Results: Itaconate attenuated liver IR injury. A total of 138 lncRNAs and 156 messenger RNAs (mRNAs) were markedly differentially expressed in the IR-damaged liver tissues pretreated with OI compared with the matched liver tissues treated with vehicle. Functional analysis indicated that lncRNAs may indirectly participate in the effects of itaconate. Furthermore, 41 mRNAs were examined for the protein–protein interaction (PPI) network analysis, and a key gene cluster was defined. Then, combined the coexpression analysis and the cis and trans regulatory function prediction of lncRNAs, some “candidate” lncRNA-mRNA pairs which might relate to itaconate-mediated liver protection were identified, while the relationship requires future validation.Conclusion: Our study revealed that itaconate could protect the liver against IR injury and that lncRNAs might play a role in this process. Our study provides a novel way to investigate the mechanism by which itaconate affects hepatic IR injury and exerts its anti-inflammatory and antioxidative stress effects.Keywords: itaconate, ischemia-reperfusion injury, liver, lncRNAhttps://www.dovepress.com/integrative-analysis-of-the-roles-of-lncrnas-and-mrnas-in-itaconate-me-peer-reviewed-fulltext-article-JIRitaconateischemia-reperfusion injuryliverlncrna |
| spellingShingle | Xu Y Li Z Lu S Wang C Ke S Li X Yin B Yu H Zhou M Pan S Jiang H Ma Y Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice Journal of Inflammation Research itaconate ischemia-reperfusion injury liver lncrna |
| title | Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice |
| title_full | Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice |
| title_fullStr | Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice |
| title_full_unstemmed | Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice |
| title_short | Integrative Analysis of the Roles of lncRNAs and mRNAs in Itaconate-Mediated Protection Against Liver Ischemia-Reperfusion Injury in Mice |
| title_sort | integrative analysis of the roles of lncrnas and mrnas in itaconate mediated protection against liver ischemia reperfusion injury in mice |
| topic | itaconate ischemia-reperfusion injury liver lncrna |
| url | https://www.dovepress.com/integrative-analysis-of-the-roles-of-lncrnas-and-mrnas-in-itaconate-me-peer-reviewed-fulltext-article-JIR |
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