Dataset Information

GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.

ABSTRACT:

Background

Acetaminophen (APAP) overdose is a significant contributor to drug-induced liver injury worldwide. G-protein-coupled receptor 116 (GPR116) is an important homeostatic maintenance molecule in the body, but little is known about its role in APAP-induced liver injury (AILI).

Methods

GPR116 expression was determined in both human and mouse AILI models. Hepatic function and damage response were analyzed in hepatocyte-specific GPR116 deletion (GPR116^△HC) mice undergoing APAP challenge. RNA-sequencing, immunofluorescence confocal, and co-immunoprecipitation (CO-IP) were employed to elucidate the impact and underlying mechanisms of GPR116 in AILI.

Results

Intrahepatic GPR116 was upregulated in human and mice with AILI. GPR116^△HC mice were vulnerable to AILI compared to wild-type mice. Overexpression of GPR116 effectively mitigated AILI in wild-type mice and counteracted the heightened susceptibility of GPR116^△HC mice to APAP. Mechanistically, GPR116 inhibits the binding immunoglobulin protein (BiP), a critical regulator of ER function, through its interaction with β-arrestin1, thereby mitigating ER stress during the early stage of AILI. Additionally, the activation of GPR116 by ligand FNDC4 has been shown to confer a protective effect against early hepatotoxicity caused by APAP in murine model.

Conclusions

Upregulation of GPR116 on hepatocytes inhibits ER stress by binding to β-arrestin1, protecting mice from APAP-induced hepatotoxicity. GPR116 may serve as a promising therapeutic target for AILI.

SUBMITTER: Xiang Q

PROVIDER: S-EPMC11335223 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.

Xiang Qian Q Li Na N Zhang Yan Y Wang Ting T Wang Ying Y Bian Jinjun J

Cellular and molecular life sciences : CMLS 20240713 1

<h4>Background</h4>Acetaminophen (APAP) overdose is a significant contributor to drug-induced liver injury worldwide. G-protein-coupled receptor 116 (GPR116) is an important homeostatic maintenance molecule in the body, but little is known about its role in APAP-induced liver injury (AILI).<h4>Methods</h4>GPR116 expression was determined in both human and mouse AILI models. Hepatic function and damage response were analyzed in hepatocyte-specific GPR116 deletion (GPR116<sup>△HC</sup>) mice under ...[more]

PMID: 39001944

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Dataset Information

GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.

Background

Methods

Results

Conclusions

Publications

GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.

Similar Datasets

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