Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization
ABSTRACTAggravated liver injury has been reported in aged ischemia/reperfusion-stressed livers; however, the mechanism of aged macrophage inflammatory regulation is not well understood. Here, we found that the adaptor protein TRIB1 plays a critical role in the differentiation of macrophages and the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-06-01
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| Series: | Bioengineered |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21655979.2022.2090218 |
| _version_ | 1811175424256901120 |
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| author | Qi Chen Yating Song Ningli Yang Xiaoming Ai Liyong Pu Lianbao Kong |
| author_facet | Qi Chen Yating Song Ningli Yang Xiaoming Ai Liyong Pu Lianbao Kong |
| author_sort | Qi Chen |
| collection | DOAJ |
| description | ABSTRACTAggravated liver injury has been reported in aged ischemia/reperfusion-stressed livers; however, the mechanism of aged macrophage inflammatory regulation is not well understood. Here, we found that the adaptor protein TRIB1 plays a critical role in the differentiation of macrophages and the inflammatory response in the liver after ischemia/reperfusion injury. In the present study, we determined that aging promoted macrophage-mediated liver injury and that inflammation was mainly responsible for lower M2 polarization in liver transplantation-exposed humans post I/R. Young and aged mice were subjected to hepatic I/R modeling and showed that aging aggravated liver injury and suppressed macrophage TRIB1 protein expression and anti-inflammatory function in I/R‐stressed livers. Restoration of TRIB1 is mediated by lentiviral infection-induced macrophage anti-inflammatory M2 polarization and alleviated hepatic I/R injury. Moreover, TRIB1 overexpression in macrophages facilitates M2 polarization and anti-inflammation by activating MEK1-ERK1/2 signaling under IL-4 stimulation. Taken together, our results demonstrated that aging promoted hepatic I/R injury by suppressing TRIB1-mediated MEK1-induced macrophage M2 polarization and anti-inflammatory function. |
| first_indexed | 2024-04-10T19:36:59Z |
| format | Article |
| id | doaj.art-c9808ca23faa4e85ba742c0ebda30d9a |
| institution | Directory Open Access Journal |
| issn | 2165-5979 2165-5987 |
| language | English |
| last_indexed | 2024-04-10T19:36:59Z |
| publishDate | 2022-06-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Bioengineered |
| spelling | doaj.art-c9808ca23faa4e85ba742c0ebda30d9a2023-01-30T05:01:59ZengTaylor & Francis GroupBioengineered2165-59792165-59872022-06-01136145191453310.1080/21655979.2022.2090218Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarizationQi Chen0Yating Song1Ningli Yang2Xiaoming Ai3Liyong Pu4Lianbao Kong5Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Bariatric and Metabolic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Bariatric and Metabolic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaABSTRACTAggravated liver injury has been reported in aged ischemia/reperfusion-stressed livers; however, the mechanism of aged macrophage inflammatory regulation is not well understood. Here, we found that the adaptor protein TRIB1 plays a critical role in the differentiation of macrophages and the inflammatory response in the liver after ischemia/reperfusion injury. In the present study, we determined that aging promoted macrophage-mediated liver injury and that inflammation was mainly responsible for lower M2 polarization in liver transplantation-exposed humans post I/R. Young and aged mice were subjected to hepatic I/R modeling and showed that aging aggravated liver injury and suppressed macrophage TRIB1 protein expression and anti-inflammatory function in I/R‐stressed livers. Restoration of TRIB1 is mediated by lentiviral infection-induced macrophage anti-inflammatory M2 polarization and alleviated hepatic I/R injury. Moreover, TRIB1 overexpression in macrophages facilitates M2 polarization and anti-inflammation by activating MEK1-ERK1/2 signaling under IL-4 stimulation. Taken together, our results demonstrated that aging promoted hepatic I/R injury by suppressing TRIB1-mediated MEK1-induced macrophage M2 polarization and anti-inflammatory function.https://www.tandfonline.com/doi/10.1080/21655979.2022.2090218Liver ischemia/reperfusion injuryinflammationmacrophageTRIB1polarization |
| spellingShingle | Qi Chen Yating Song Ningli Yang Xiaoming Ai Liyong Pu Lianbao Kong Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization Bioengineered Liver ischemia/reperfusion injury inflammation macrophage TRIB1 polarization |
| title | Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization |
| title_full | Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization |
| title_fullStr | Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization |
| title_full_unstemmed | Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization |
| title_short | Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization |
| title_sort | aging deteriorated liver ischemia and reperfusion injury by suppressing tribble s proteins 1 mediated macrophage polarization |
| topic | Liver ischemia/reperfusion injury inflammation macrophage TRIB1 polarization |
| url | https://www.tandfonline.com/doi/10.1080/21655979.2022.2090218 |
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