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 |
| Published: |
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 |
| Summary: | 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. |
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| ISSN: | 2165-5979 2165-5987 |