MSR1-dependent efferocytosis improved ischemia-reperfusion injury following aged-donor liver transplantation in mice by regulating the pro-resolving polarisation of macrophages.

Autor: Xu XS; Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China., Liu T; Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China., Chen YJ; Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China., Wu XY; Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China., Cheng MX; Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: 305258@hospital.cqmu.edu.cn., Li JZ; Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: 303234@hospital.cqmu.edu.cn.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2024 Sep 01; Vol. 442 (1), pp. 114212. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1016/j.yexcr.2024.114212
Abstrakt: Compared with young liver donors, aged liver donors are more susceptible to ischemia-reperfusion injury (IRI) following transplantation, which may be related to excessive inflammatory response and macrophage dysfunction, but the specific mechanism is unclear. Macrophage scavenger receptor 1 (MSR1) is a member of the scavenger receptor family, and plays an important regulatory role in inflammation response and macrophage function regulation. But its role in IRI following aged-donor liver transplantation is still unclear. This study demonstrates that MSR1 expression is decreased in macrophages from aged donor livers, inhibiting their efferocytosis and pro-resolving polarisation. Decreased MSR1 is responsible for the more severe IRI suffered by aged donor livers. Overexpression of MSR1 using F4/80-labelled AAV 9 improved intrahepatic macrophage efferocytosis and promoted pro-resolving polarisation, ultimately ameliorating IRI following aged-donor liver transplantation. In vitro co-culture experiments further showed that overexpression of MSR1 promoted an increase in calcium concentration, which further activated the PI3K-AKT-GSK3β pathway, and induced the upregulation of β-catenin. Overall, MSR1-dependent efferocytosis promoted the pro-resolving polarisation of macrophages through the PI3K-AKT-GSK3β pathway-induced up-regulating of β-catenin leading to improved IRI following aged-donor liver transplantation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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