Molecular characterization and functional exploration of GPR84 in Chinese Giant Salamander (Andrias davidianus). (December 2022)

• Record Type: Journal Article
• Authors: Yu, Hui-Xia; Li, Yang; Ezeorba, Timothy; Mo, Hao-Lin; Zhang, Zhi-Hao; Yang, Qi-Yuan; Wang, Li-Xin
• Is Part Of: Developmental and comparative immunology. Volume 137(2022)
• Publication Date: 2022-12
• Subjects: Chinese Giant Salamander -- GPR84 -- MCFAs -- Signaling -- Immune modulator; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2022.104526
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: 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 gpr 84 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. Highlights: -Chinese giant salamander GPR84 contains an open reading frame of 1131 bp encoding a putative protein of 376 amino acids. The gpr8 4 has the highest expression in the kidney and liver. The GPR84 can activate cAMP and extracellular signal-regulated kinase 1/2 signaling pathways. Activation of GPR84 by medium-chain fatty acids upregulates the expression of NF-kappa B and IL-6.