Department of Internal Medicine, Chonnam National University Medical School, Gwangju, 61469, Korea.
Exp Mol Med. 2023 Feb;55(2):304-312. doi: 10.1038/s12276-023-00932-2. Epub 2023 Feb 3.
The prevalence of kidney diseases has been increasing worldwide due to the aging population and has results in an increased socioeconomic burden as well as increased morbidity and mortality. A deep understanding of the mechanisms underlying the physiological regulation of the kidney and the pathogenesis of related diseases can help identify potential therapeutic targets. The farnesoid X receptor (FXR, NR1H4) is a primary nuclear bile acid receptor that transcriptionally regulates bile acid homeostasis as well as glucose and lipid metabolism in multiple tissues. The roles of FXR in tissues other than hepatic and intestinal tissues are poorly understood. In studies over the past decade, FXR has been demonstrated to have a protective effect against kidney diseases through its anti-inflammatory and antifibrotic effects; it also plays roles in glucose and lipid metabolism in the kidney. In this review, we discuss the physiological role of FXR in the kidney and its pathophysiological roles in various kidney diseases, including acute kidney injury and chronic kidney diseases, diabetic nephropathy, and kidney fibrosis. Therefore, the regulatory mechanisms involving nuclear receptors, such as FXR, in the physiology and pathophysiology of the kidney and the development of agonists and antagonists for modulating FXR expression and activation should be elucidated to identify therapeutic targets for the treatment of kidney diseases.
由于人口老龄化,全球范围内肾脏疾病的患病率不断增加,这不仅导致了社会经济负担的加重,还增加了发病率和死亡率。深入了解肾脏生理调节和相关疾病发病机制的机制,可以帮助确定潜在的治疗靶点。法尼醇 X 受体 (FXR,NR1H4) 是一种主要的核胆汁酸受体,可在多种组织中转录调节胆汁酸稳态以及葡萄糖和脂质代谢。FXR 在肝和肠组织以外的组织中的作用尚未得到充分了解。在过去十年的研究中,已经证明 FXR 通过其抗炎和抗纤维化作用对肾脏疾病具有保护作用;它在肾脏中的葡萄糖和脂质代谢中也发挥作用。在这篇综述中,我们讨论了 FXR 在肾脏中的生理作用及其在各种肾脏疾病中的病理生理作用,包括急性肾损伤和慢性肾脏病、糖尿病肾病和肾脏纤维化。因此,应该阐明涉及核受体(如 FXR)的调节机制在肾脏生理学和病理学中的作用,以及开发激动剂和拮抗剂来调节 FXR 表达和激活,以确定治疗肾脏疾病的治疗靶点。