Yao Ming-Xing, Yu Hui-Xia, Mo Hao-Lin, Zhang Zhi-Hao, Song Qing-Chuan, Liu Qiao, Yang Qi-Yuan, Wang Li-Xin, Li Yang
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Department of Pathology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, 710038, China.
Dev Comp Immunol. 2024 Apr;153:105126. doi: 10.1016/j.dci.2023.105126. Epub 2023 Dec 29.
The medium-chain fatty acid receptor GPR84, a member of the G protein-coupled receptor family, is mainly expressed in macrophages and microglia, and is involved in the regulation of inflammatory responses and retinal development in mammals and amphibians. However, structure, tissue distribution, and pharmacology of this receptor have rarely been reported in fish. In this study, we cloned the coding sequence (CDS) of common carp GPR84 (ccGPR84), examined its tissue distribution, and explored its cellular signaling function. The results showed that the CDS of ccGPR84 is 1191 bp and encodes a putative protein with 396 amino acids. Phylogenetic and chromosomal synteny analyses revealed that ccGPR84 was evolutionarily conserved with Cyprinids. Real-time quantitative PCR (qPCR) indicated that ccGPR84 was predominantly expressed in the intestine and spleen. Luciferase reporter assay demonstrated that nonanoic acid, capric acid (decanoic acid), undecanoic acid and lauric acid could inhibit cAMP signaling pathway and activate MAPK/ERK signaling pathway, while the potencies of these four fatty acids on the two signaling pathways were different. Lauric acid has the highest inhibitory potency on cAMP signaling pathway, followed by undecanoic acid, nonanoic acid, and capric acid. While for MAPK/ERK signaling pathway, nonanoic acid has the highest activation potency, followed by undecanoic acid, capric acid, and lauric acid. These findings lay the foundation for revealing the roles of different medium-chain fatty acids in the inflammatory response of common carp.
中链脂肪酸受体GPR84是G蛋白偶联受体家族的一员，主要在巨噬细胞和小胶质细胞中表达，参与哺乳动物和两栖动物炎症反应的调节以及视网膜发育。然而，该受体在鱼类中的结构、组织分布和药理学研究鲜有报道。在本研究中，我们克隆了鲤鱼GPR84（ccGPR84）的编码序列（CDS），检测了其组织分布，并探究了其细胞信号功能。结果显示，ccGPR84的CDS为1191 bp，编码一个含有396个氨基酸的假定蛋白。系统发育和染色体共线性分析表明，ccGPR84在鲤科鱼类中具有进化保守性。实时定量PCR（qPCR）表明，ccGPR84主要在肠道和脾脏中表达。荧光素酶报告基因检测表明，壬酸、癸酸、十一酸和月桂酸可抑制cAMP信号通路并激活MAPK/ERK信号通路，而这四种脂肪酸对这两条信号通路的作用强度不同。月桂酸对cAMP信号通路的抑制作用最强，其次是十一酸、壬酸和癸酸。而对于MAPK/ERK信号通路，壬酸的激活作用最强，其次是十一酸、癸酸和月桂酸。这些发现为揭示不同中链脂肪酸在鲤鱼炎症反应中的作用奠定了基础。
