Calorie restriction mimetic, resveratrol, attenuates hepatic ischemia and reperfusion injury through enhancing efferocytosis of macrophages via AMPK/STAT3/S1PR1 pathway.

Autor: Yao X; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China., Liu Y; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China., Mao M; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China., Yang L; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address: lqyang72721@126.com., Zhan Q; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address: zhanqionghui328@163.com., Xiao J; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address: applexiaomz@163.com.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2024 Apr; Vol. 126, pp. 109587. Date of Electronic Publication: 2024 Jan 21.
DOI: 10.1016/j.jnutbio.2024.109587
Abstrakt: Calorie restriction (CR) mimetic, resveratrol (RSV), has the capacity of promoting phagocytosis. However, its role in hepatic ischemia and reperfusion injury (HIRI) remains poorly understood. This study aimed to investigate the effect of RSV on alleviating HIRI and explore the underlying mechanisms. RSV was intraperitoneally injected in mice HIRI model, while RSV was co-incubated with culture medium for 24 h in RAW 264.7 cells and kupffer cells. Macrophage efferocytosis was assessed by immunostaining of PI and F4/80. The clearance of apoptotic neutrophils in the liver was determined by immunostaining of Ly6-G and cleaved-caspase-3. HE staining, Suzuki's score, serum levels of ALT, AST, TNF-α and IL-1β were analyzed to evaluate HIRI. The efferocytosis inhibitor, Cytochalasin D, was utilized to investigate the effect of RSV on HIRI. Western blot was employed to measure the levels of AMPKα, phospho-AMPKα, STAT3, phospho-STAT3 and S1PR1. SiSTAT3 and inhibitors targeting AMPK, STAT3 and S1PR1, respectively, were used to confirm the involvement of AMPK/STAT3/S1PR1 pathway in RSV-mediated efferocytosis and HIRI. RSV facilitated the clearance of apoptotic neutrophils and attenuated HIRI, which was impeded by Cytochalasin D. RSV boosted macrophage efferocytosis by up-regulating the levels of phospho-AMPKα, phospho-STAT3 and S1PR1, which was reversed by AMPK, STAT3 and S1PR1 inhibitors, respectively. Inhibition of STAT3 suppressed RSV-induced clearance of apoptotic neutrophils and exacerbated HIRI. CR mimetic, RSV, alleviates HIRI by promoting macrophages efferocytosis through AMPK/STAT3/S1PR1 pathway, providing valuable insights into the mechanisms underlying the protective effects of CR on attenuating HIRI.
Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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