College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Enugu, 0023442, Nigeria.
Dev Comp Immunol. 2022 Dec;137:104526. doi: 10.1016/j.dci.2022.104526. Epub 2022 Sep 1.
The G protein-coupled receptor 84 (GPR84) is a putative medium-chain fatty acids (MCFAs) receptor involved in immune regulation and other metabolic processes. Most available studies focused on the GPR84 characterization from mammals, neglecting vital information that could be obtained from other levels of life, such as amphibians, necessary for an apt evolutionary understanding of the orphan GPR84. Hence, this study molecularly characterized and functionally explored the GPR84 from the Chinese Giant Salamander (Andrias davidianus). Therefore, we report that the Chinese Giant Salamander (CGS), one of the world's largest amphibians, expresses a GPR84 protein having 376 amino acids, with about 70% homologous to other amphibians and around 50% to human GPR84. Investigating the relative localized expression of gpr84 mRNA in CGS using quantitative PCR revealed the highest expression in the kidney and liver. Furthermore, four medium-chain fatty acids (MCFAs) at micromolar levels activated CGS-GPR84 transfected and expressed in HEK293 cells. In HEK293 cells, four different concentrations of MCFAs inhibited forskolin-induced cAMP accumulation and resulted in a dose-dependent increase in extracellular signal-regulated kinases 1 and 2 (ERK1/2). Interestingly, MCFAs activation of GPR84 concomitantly led to the upregulation of inflammatory mediators such as Nuclear Factor Kappa B (NF-κB) and IL-6. Conclusively, this study successfully elucidated the intriguing molecular and functional properties of CGS GPR84, particularly as an immune modulator, and has positioned the findings within the existing body of knowledge for a better overall understanding of GPR84, especially in amphibians.
G 蛋白偶联受体 84（GPR84）是一种假定的中链脂肪酸（MCFAs）受体，参与免疫调节和其他代谢过程。大多数可用的研究都集中在哺乳动物的 GPR84 特征描述上，忽略了从其他生命层次（如两栖动物）获得的重要信息，而这些信息对于适当的 GPR84 进化理解是必要的。因此，本研究从中国大鲵（Andrias davidianus）分子特征和功能探索了 GPR84。因此，我们报告称，中国大鲵（CGS）是世界上最大的两栖动物之一，表达一种具有 376 个氨基酸的 GPR84 蛋白，与其他两栖动物约有 70%同源，与人类 GPR84 约有 50%同源。使用定量 PCR 研究 CGS 中 gpr84 mRNA 的相对局部表达，发现肾脏和肝脏中的表达最高。此外，四种微摩尔水平的中链脂肪酸（MCFAs）激活了在 HEK293 细胞中转染和表达的 CGS-GPR84。在 HEK293 细胞中，四种不同浓度的 MCFAs 抑制了 forskolin诱导的 cAMP 积累，并导致细胞外信号调节激酶 1 和 2（ERK1/2）的剂量依赖性增加。有趣的是，MCFAs 激活 GPR84 同时导致核因子 kappa B（NF-κB）和 IL-6 等炎症介质的上调。总之，本研究成功阐明了 CGS GPR84 引人入胜的分子和功能特性，特别是作为免疫调节剂，并将研究结果置于现有知识体系内，以更好地理解 GPR84，特别是在两栖动物中。
