Research Paper Volume 13, Issue 18 pp 22588—22610
GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis
- 1 Department of Pharmacy, Second Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China
- 2 Department of Pharmacology, College of Pharmacy, Wannan Medical College, Wuhu 241002, Anhui, China
- 3 Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, China
- 4 State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China
Received: July 5, 2021 Accepted: September 7, 2021 Published: September 28, 2021https://doi.org/10.18632/aging.203572
How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sepsis is a common critical illness in ICU and always a great difficulty in clinical treatment. GPR43 (G protein-coupled receptor 43) participates in regulating appetite and gastrointestinal peptide secretion to modulate fat decomposition and formation. However, the biological contribution of GPR43 on inflammation of sepsis has not been previously investigated. We investigated the mechanisms of GPR43 gene, which plays a possible role in distinguishing sepsis and contributes to the pathogenesis of sepsis-induced inflammatory reaction. Furthermore, we performed studies with mice induced to sepsis by Cecal Ligation and Puncture (CLP), Knockout GPR43 (GPR43-/-) mice, and Wild Type (WT) mice induced with CLP. In addition, lung tissues and cell samples were analyzed by histology, Quantitative Polymerase Chain Reaction (Q-PCR), Enzyme-linked Immunosorbent (ELISA) Assay, and western blot. GPR43 agonist could significantly reduce inflammation reactions and trigger lung injury in mice with sepsis. As for GPR43-/- mice, the risks of sepsis-induced inflammatory reactions and corresponding lung injury were promoted. On the one hand, the up-regulation of GPR43 gene reduced ROS mitochondrial damage to inhibit inflammatory reactions via the inactivation of NLRP3 Inflammasome by PPARγ/ Nox1/EBP50/ p47phox signal channel. On the other hand, the down-regulation of GPR43 promoted inflammatory reactions in vitro model through the acceleration of ROS-dependently mitochondrial damage by PPARγ/ Nox1/EBP50/ p47phox/ NLRP3 signal channel. These findings indicate that the inhibition of GPR43 as a possible important factor of sepsis may shed lights on the mechanism of sepsis-induced inflammation reaction.