The UTS2R gene encodes for the urotensin II receptor (UTS2R), which is a member of the G-protein coupled receptor (GPCR) superfamily. GPCRs are integral membrane proteins that are involved in a wide range of physiological processes, including signal transduction, cell differentiation, and development. UTS2R is specifically activated by urotensin II (UTS2), a peptide hormone that is found in vertebrates. The UTS2/UTS2R signaling pathway has been implicated in several biological processes, including cardiovascular function, inflammation, and cell migration[1,2,3,4,5,6,7,8].

One of the most well-studied roles of UTS2R is its involvement in cardiovascular function. UTS2R activation has been shown to cause vasoconstriction, which is the narrowing of blood vessels. This can lead to an increase in blood pressure and is thought to be a contributing factor in the development of cardiovascular diseases, such as hypertension and heart failure. Additionally, UTS2R activation has been shown to have inotropic effects, meaning it can affect the contractility of the heart[4]. These effects suggest that UTS2R may be a potential target for the treatment of cardiovascular diseases.

UTS2R has also been implicated in inflammation. Activation of UTS2R has been shown to increase the expression of inflammatory cytokines, such as interleukin-6 (IL-6), and to promote the recruitment of immune cells to sites of inflammation. This suggests that UTS2R may play a role in the development of inflammatory diseases, such as arthritis and asthma[3,5].

In addition to its role in cardiovascular function and inflammation, UTS2R has also been implicated in cell migration. Activation of UTS2R has been shown to promote the migration of cells, such as immune cells and cancer cells. This suggests that UTS2R may play a role in the development of diseases that involve cell migration, such as cancer metastasis[3,6,8].

The UTS2/UTS2R signaling pathway has also been implicated in the development of idiopathic scoliosis, a condition characterized by an abnormal curvature of the spine. Mutations in the UTS2R gene have been associated with an increased risk of adolescent idiopathic scoliosis (AIS), suggesting that UTS2R may play a role in the development of this condition[1].

UTS2R has also been shown to be involved in the regulation of glucose metabolism and insulin resistance, which are important factors in the development of type 2 diabetes mellitus (T2DM). Mutations in the UTS2R gene have been associated with alterations in fatty acid composition and fat accumulation in skeletal muscle, suggesting that UTS2R may play a role in the development of obesity and T2DM[5,6].

Finally, UTS2R has been shown to play a role in the development of subarachnoid hemorrhage (SAH), a condition characterized by bleeding in the space between the brain and the skull. UTS2R activation has been shown to trigger an early meningeal response and a delayed macrophage-dependent vasospasm after SAH, which can lead to cognitive dysfunction. This suggests that UTS2R may be a potential target for the treatment of SAH[7].

In conclusion, UTS2R is a GPCR that is involved in a wide range of physiological processes, including cardiovascular function, inflammation, and cell migration. UTS2R has been implicated in the development of several diseases, including idiopathic scoliosis, type 2 diabetes mellitus, and subarachnoid hemorrhage. Further research is needed to fully understand the role of UTS2R in these diseases and to develop potential therapeutic targets for their treatment.

References:

1. Dai, Zhicheng, Wang, Yuwen, Wu, Zhichong, Xu, Leilei, Zhu, Zezhang. . Novel Mutations in UTS2R are Associated with Adolescent Idiopathic Scoliosis in the Chinese Population. In Spine, 46, E288-E293. doi:10.1097/BRS.0000000000003786. https://pubmed.ncbi.nlm.nih.gov/33156271/

2. Selinger, Martin, Věchtová, Pavlína, Tykalová, Hana, Štěrba, Ján, Grubhoffer, Libor. 2022. Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors. In Computational and structural biotechnology journal, 20, 2759-2777. doi:10.1016/j.csbj.2022.05.052. https://pubmed.ncbi.nlm.nih.gov/35685361/

3. Tostivint, Hervé, Ocampo Daza, Daniel, Bergqvist, Christina A, Lihrmann, Isabelle, Larhammar, Dan. 2014. Molecular evolution of GPCRs: Somatostatin/urotensin II receptors. In Journal of molecular endocrinology, 52, T61-86. doi:10.1530/JME-13-0274. https://pubmed.ncbi.nlm.nih.gov/24740737/

4. Ogawa, Akiko, Ohira, Seiya, Kato, Yuri, Inoue, Asuka, Wei, Fan-Yan. 2023. Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction. In Communications biology, 6, 511. doi:10.1038/s42003-023-04888-x. https://pubmed.ncbi.nlm.nih.gov/37173432/

5. Jiang, Zhihua, Michal, Jennifer J, Tobey, David J, Macneil, Michael D, Magnuson, Nancy S. 2008. Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus. In International journal of biological sciences, 4, 96-102. doi:. https://pubmed.ncbi.nlm.nih.gov/18463714/

6. Sasazaki, Shinji, Akiyama, Kento, Narukami, Takahiro, Oyama, Kenji, Mannen, Hideyuki. . UTS2R gene polymorphisms are associated with fatty acid composition in Japanese beef cattle. In Animal science journal = Nihon chikusan Gakkaiho, 85, 499-505. doi:. https://pubmed.ncbi.nlm.nih.gov/24851282/

7. Carotenuto, A, Grieco, P, Rovero, P, Novellino, E. . Urotensin-II receptor antagonists. In Current medicinal chemistry, 13, 267-75. doi:. https://pubmed.ncbi.nlm.nih.gov/16475936/

8. Pedard, Martin, Prevost, Lucie, Carpena, Camille, Vivien, Denis, Castel, Hélène. 2024. The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice. In Nature communications, 15, 8430. doi:10.1038/s41467-024-52654-2. https://pubmed.ncbi.nlm.nih.gov/39341842/