Michael Olugbenga S, Kanthakumar Praghalathan, Soni Hitesh, Rajesh Lenin Raji, Abhiram Jha Kumar, Gangaraju Rajashekhar, Adebiyi Adebowale
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
Curr Res Physiol. 2024 May 7;7:100126. doi: 10.1016/j.crphys.2024.100126. eCollection 2024.
Chronic kidney disease (CKD) is a progressive and long-term condition marked by a gradual decline in kidney function. CKD is prevalent among those with conditions such as diabetes mellitus, hypertension, and glomerulonephritis. Affecting over 10% of the global population, CKD stands as a significant cause of morbidity and mortality. Despite substantial advances in understanding CKD pathophysiology and management, there is still a need to explore novel mechanisms and potential therapeutic targets. Urotensin II (UII), a potent vasoactive peptide, has garnered attention for its possible role in the development and progression of CKD. The UII system consists of endogenous ligands UII and UII-related peptide (URP) and their receptor, UT. URP pathophysiology is understudied, but alterations in tissue expression levels of UII and UT and blood or urinary UII concentrations have been linked to cardiovascular and kidney dysfunctions, including systemic hypertension, chronic heart failure, glomerulonephritis, and diabetes. UII gene polymorphisms are associated with increased risk of diabetes. Pharmacological inhibition or genetic ablation of UT mitigated kidney and cardiovascular disease in rodents, making the UII system a potential target for slowing CKD progression. However, a deeper understanding of the UII system's cellular mechanisms in renal and extrarenal organs is essential for comprehending its role in CKD pathophysiology. This review explores the evolving connections between the UII system and CKD, addressing potential mechanisms, therapeutic implications, controversies, and unexplored concepts.
慢性肾脏病（CKD）是一种渐进性的长期病症，其特征是肾功能逐渐下降。CKD在患有糖尿病、高血压和肾小球肾炎等疾病的人群中普遍存在。CKD影响着全球超过10%的人口，是发病和死亡的重要原因。尽管在理解CKD病理生理学和管理方面取得了重大进展，但仍有必要探索新的机制和潜在的治疗靶点。尾加压素II（UII）是一种强效血管活性肽，因其在CKD发生和发展中的可能作用而受到关注。UII系统由内源性配体UII和UII相关肽（URP）及其受体UT组成。URP的病理生理学研究较少，但UII和UT的组织表达水平以及血液或尿液中UII浓度的改变与心血管和肾脏功能障碍有关，包括系统性高血压、慢性心力衰竭、肾小球肾炎和糖尿病。UII基因多态性与糖尿病风险增加有关。在啮齿动物中，对UT进行药理学抑制或基因敲除可减轻肾脏和心血管疾病，这使得UII系统成为减缓CKD进展的潜在靶点。然而，深入了解UII系统在肾脏和肾外器官中的细胞机制对于理解其在CKD病理生理学中的作用至关重要。本综述探讨了UII系统与CKD之间不断演变的联系，阐述了潜在机制、治疗意义、争议和未探索的概念。
