Uts2, also known as urotensin II, is an undecapeptide hormone and the most potent vasoconstrictor identified so far [4]. It has a highly conserved structure through mammalian phylogeny. Although its precise role in physiology and disease is still being explored, it has been implicated in various processes. Uts2 may function within autocrine and paracrine systems and is associated with pathways related to vasoconstriction, fibrosis, and potentially immune regulation [4,3]. Genetic models can be valuable in further elucidating its functions.

In Behçet's disease, the Thr/Thr genotype and the Thr allele of Uts2 rs228648 variant were significantly more frequent in patients compared to normal controls, suggesting a role in the development and clinical modulation of the disease [1]. In colon cancer, Uts2 was part of a five-immune gene prognostic risk model, which was an independent prognostic variable more accurate than age and pathological stage in predicting overall survival at five years [2]. In glioblastoma multiforme, knockdown of Uts2 led to decreased cell proliferation and migration, and in vivo studies showed it suppressed xenograft growth, indicating its tumor-promoting effects [3]. In Kawasaki disease, host genetics influenced Uts2 levels, which may contribute to inflammation and cardiovascular damage [5]. In the Chinese population, the Ser89Asn polymorphisms of the Uts2 gene were associated with atrial fibrillation, and the Met21Met genotype may have a potential beneficial role [6].

In conclusion, Uts2 plays important roles in multiple disease conditions, including autoimmune diseases, cancers, and cardiovascular-related diseases. The use of loss-of-function models, such as knockdown in glioblastoma, has revealed its tumor-promoting effects. These studies contribute to understanding the mechanisms of disease development and may provide potential targets for therapeutic intervention.

References:

1. Kamal, Asmaa, Elgengehy, Fatema T, Elawady, Zahraa, Fawzy, Nahla A, El Sisi, Ola. 2021. Role of miR-146a rs2910164 and UTS2 rs228648 Genetic Variants in Behçet's Disease. In Immunological investigations, 51, 899-908. doi:10.1080/08820139.2021.1883647. https://pubmed.ncbi.nlm.nih.gov/33605830/

2. Chen, Haitao, Luo, Jun, Guo, Jianchun. 2020. Development and validation of a five-immune gene prognostic risk model in colon cancer. In BMC cancer, 20, 395. doi:10.1186/s12885-020-06799-0. https://pubmed.ncbi.nlm.nih.gov/32375704/

3. Wang, Yanfei, Shen, Langping, Sun, Mingzhong. 2024. Prognostic Significance and Functional Mechanism of UTS2 in Glioblastoma Multiforme. In Current cancer drug targets, , . doi:10.2174/0115680096275291231226081320. https://pubmed.ncbi.nlm.nih.gov/38265405/

4. Langham, Robyn G, Kelly, Darren J. . Urotensin II and the kidney. In Current opinion in nephrology and hypertension, 22, 107-12. doi:10.1097/MNH.0b013e32835b6d57. https://pubmed.ncbi.nlm.nih.gov/23197158/

5. Huang, Cassidy Y, Burns, Jane C, Shimizu, Chisato. 2017. Urotensin 2 in Kawasaki disease pathogenesis. In Pediatric research, 82, 1048-1055. doi:10.1038/pr.2017.183. https://pubmed.ncbi.nlm.nih.gov/28753597/

6. Zhao, Jing, Ding, Wen-Hui, Chu, Song-Yun, Xia, Yu-Long, Wu, Lin. 2016. Role of UTS2 gene in the genetic susceptibility to atrial fibrillation in the Chinese population. In Postgraduate medical journal, 92, 201-7. doi:10.1136/postgradmedj-2015-133699. https://pubmed.ncbi.nlm.nih.gov/26811505/