Felsenstein Medical Research Center, Tel-Aviv University.
Department of Nephrology and Hypertension, Rabin Medical Center, Sackler School of Medicine, Tel-Aviv University, Petah Tikva.
Curr Opin Nephrol Hypertens. 2018 Jan;27(1):56-62. doi: 10.1097/MNH.0000000000000374.
Bile acids act as activating signals of endogenous renal receptors: the nuclear receptor farnesoid X receptor (FXR) and the membrane-bound G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). In recent years, bile acids have emerged as important for renal pathophysiology by activating FXR and TGR5 and transcription factors relevant for lipid, cholesterol and carbohydrate metabolism, as well as genes involved in inflammation and renal fibrosis.
Activation of bile acid receptors has a promising therapeutic potential in prevention of diabetic nephropathy and obesity-induced renal damage, as well as in nephrosclerosis. During the past decade, progress has been made in understanding the biology and mechanisms of bile acid receptors in the kidney and in the development of specific bile acid receptor agonists.
In this review, we discuss current knowledge on the roles of FXR and TGR5 in the physiology of the kidney and the latest advances made in development and characterization of bile acid analogues that activate bile acid receptors for treatment of renal disease.
胆汁酸作为内源性肾脏受体的激活信号发挥作用:核受体法尼醇 X 受体(FXR)和膜结合 G 蛋白偶联胆汁酸受体 1(GPBAR1,也称为 TGR5)。近年来,胆汁酸通过激活 FXR 和 TGR5 以及与脂质、胆固醇和碳水化合物代谢相关的转录因子,以及参与炎症和肾纤维化的基因,在肾脏病理生理学中显现出重要作用。
胆汁酸受体的激活在预防糖尿病肾病和肥胖引起的肾损伤以及肾硬化症方面具有有前景的治疗潜力。在过去十年中,人们在理解肾脏中胆汁酸受体的生物学和机制以及开发特定的胆汁酸受体激动剂方面取得了进展。
在这篇综述中,我们讨论了 FXR 和 TGR5 在肾脏生理学中的作用以及开发和表征激活胆汁酸受体治疗肾脏疾病的胆汁酸类似物的最新进展。