Abstract:
The kidney is the key organ responsible for maintaining the body\'s water and electrolyte homeostasis. About 99% of the primary urine filtered from the Bowman\'s capsule is reabsorbed along various renal tubules every day, with only 1-2 L of urine excreted. Aquaporins (AQPs) play a vital role in water reabsorption in the kidney. Currently, a variety of molecules are found to be involved in the process of urine concentration by regulating the expression or activity of AQPs, such as antidiuretic hormone, renin-angiotensin-aldosterone system (RAAS), prostaglandin, and several nuclear receptors. As the main bile acid receptors, farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor 1 (TGR5) play important roles in bile acid, glucose, lipid, and energy metabolism. In the kidney, FXR and TGR5 exhibit broad expression across all segments of renal tubules, and their activation holds significant therapeutic potential for numerous acute and chronic kidney diseases through alleviating renal lipid accumulation, inflammation, oxidative stress, and fibrosis. Emerging evidence has demonstrated that the genetic deletion of FXR or TGR5 exhibits increased basal urine output, suggesting that bile acid receptors play a critical role in urine concentration. Here, we briefly summarize the function of bile acid receptors in renal water reabsorption and urine concentration.
摘要:
肾脏是负责维持人体水和电解质稳态的关键器官。从Bowman胶囊中过滤的初级尿液约有99%每天沿各种肾小管重新吸收,只有1-2升尿液排出。水通道蛋白(AQP)在肾脏的水重吸收中起着至关重要的作用。目前,发现多种分子通过调节AQPs的表达或活性参与尿液浓缩过程,如抗利尿激素,肾素-血管紧张素-醛固酮系统(RAAS),前列腺素,和几个核受体。作为主要的胆汁酸受体,法尼醇X受体(FXR)和膜G蛋白偶联胆汁酸受体1(TGR5)在胆汁酸,葡萄糖,脂质,和能量代谢。在肾脏,FXR和TGR5在肾小管的所有节段中表现出广泛的表达,它们的激活通过减轻肾脏脂质积累对许多急性和慢性肾脏疾病具有重要的治疗潜力,炎症,氧化应激,和纤维化。新的证据表明,FXR或TGR5的基因缺失表现出增加的基础尿量,提示胆汁酸受体在尿液浓度中起关键作用。这里,我们简要总结了胆汁酸受体在肾脏水分再吸收和尿液浓度中的作用。