Gpr22, an orphan G protein-coupled receptor (GPCR), is mainly expressed in the brain and heart [3]. It constitutively couples to G(i)/G(o), inhibiting adenyl cyclase [3]. Gpr22 may be involved in multiple biological processes. Cilia, important eukaryotic organelles, have their length and structure regulated by Gpr22 in zebrafish Kupffer's vesicle, which is crucial for left-right axis formation [2].

In mice, cardiomyocyte-specific overexpression of Gpr22 ameliorates cardiac injury in acute myocardial infarction (AMI) models. Myocardial ischemic stress downregulates Gpr22, while its overexpression upregulates Akt signaling, downregulates ERK activation, and mitigates ischemia-induced myocardial injury [1]. In a different context, the loss of Gpr22 expression in mice increases susceptibility to heart failure post-ventricular pressure overload, suggesting its protective role in mechanical cardiac stress [1].

In summary, Gpr22 plays a protective role in the heart against ischemic and mechanical stress, likely through the regulation of Akt and ERK signaling pathways. The study of Gpr22 using mouse models has provided valuable insights into its function in cardiac-related disease conditions, which may contribute to the development of new therapeutic strategies for heart diseases [1].

References:

1. Chang, Chin-Chuan, Chen, Chih-Hung, Hsu, Shu-Yuan, Leu, Steve. 2024. Cardiomyocyte-specific overexpression of GPR22 ameliorates cardiac injury in mice with acute myocardial infarction. In BMC cardiovascular disorders, 24, 287. doi:10.1186/s12872-024-03953-5. https://pubmed.ncbi.nlm.nih.gov/38816768/

2. Verleyen, Daphne, Luyten, Frank P, Tylzanowski, Przemko. 2014. Orphan G-protein coupled receptor 22 (Gpr22) regulates cilia length and structure in the zebrafish Kupffer's vesicle. In PloS one, 9, e110484. doi:10.1371/journal.pone.0110484. https://pubmed.ncbi.nlm.nih.gov/25335082/

3. Adams, John W, Wang, Jianming, Davis, James R, Chien, Ken, Connolly, Daniel. 2008. Myocardial expression, signaling, and function of GPR22: a protective role for an orphan G protein-coupled receptor. In American journal of physiology. Heart and circulatory physiology, 295, H509-21. doi:10.1152/ajpheart.00368.2008. https://pubmed.ncbi.nlm.nih.gov/18539757/