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      Nuclear receptors in renal health and disease

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          Summary

          As a major social and economic burden for the healthcare system, kidney diseases contribute to the constant increase of worldwide deaths. A deeper understanding of the underlying mechanisms governing the etiology, development and progression of kidney diseases may help to identify potential therapeutic targets. As a superfamily of ligand-dependent transcription factors, nuclear receptors (NRs) are critical for the maintenance of normal renal function and their dysfunction is associated with a variety of kidney diseases. Increasing evidence suggests that ligands for NRs protect patients from renal ischemia/reperfusion (I/R) injury, drug-induced acute kidney injury (AKI), diabetic nephropathy (DN), renal fibrosis and kidney cancers. In the past decade, some breakthroughs have been made for the translation of NR ligands into clinical use. This review summarizes the current understanding of several important NRs in renal physiology and pathophysiology and discusses recent findings and applications of NR ligands in the management of kidney diseases.

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          Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes

          Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown.
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            Identification of a nuclear receptor for bile acids.

            Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.
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              Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes

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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                03 February 2022
                February 2022
                03 February 2022
                : 76
                : 103855
                Affiliations
                [a ]Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China
                [b ]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
                [c ]Dalian Key Laboratory for Nuclear Receptors in Major Metabolic Diseases, Dalian, Liaoning 116044, China
                [d ]Health Science Center, East China Normal University, Shanghai 200241, China
                Author notes
                [* ]Corresponding author. xyzhang@ 123456hsc.ecnu.edu.cn
                [** ]Corresponding author at: Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China. guanyf@ 123456dmu.edu.cn
                [1]

                These authors contributed equally to this work.

                Article
                S2352-3964(22)00039-1 103855
                10.1016/j.ebiom.2022.103855
                8819107
                35123268
                d976d90f-86d0-42ad-8d26-b2e2f7974c4f
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 29 November 2021
                : 31 December 2021
                : 18 January 2022
                Categories
                Review

                kidney,ppar,mr,lxr,fxr
                kidney, ppar, mr, lxr, fxr

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