Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1905103 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2011 | 7 Pages |
Diabetes is the leading cause of end-stage renal disease in developed countries. In spite of excellent glucose and blood pressure control, including administration of angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, diabetic nephropathy still develops and progresses. The development of additional protective therapeutic interventions is, therefore, a major priority. Nuclear hormone receptors regulate carbohydrate metabolism, lipid metabolism, the immune response, and inflammation. These receptors also modulate the development of fibrosis. As a result of their diverse biological effects, nuclear hormone receptors have become major pharmaceutical targets for the treatment of metabolic diseases. The increasing prevalence of diabetic nephropathy has led intense investigation into the role that nuclear hormone receptors may have in slowing or preventing the progression of renal disease. This role of nuclear hormone receptors would be associated with improvements in metabolism, the immune response, and inflammation. Several nuclear receptor activating ligands (agonists) have been shown to have a renal protective effect in the context of diabetic nephropathy. This review will discuss the evidence regarding the beneficial effects of the activation of several nuclear, especially the vitamin D receptor (VDR), farnesoid X receptor (FXR), and peroxisome-proliferator-associated receptors (PPARs) in preventing the progression of diabetic nephropathy and describe how the discovery and development of compounds that modulate the activity of nuclear hormone receptors may provide potential additional therapeutic approaches in the management of diabetic nephropathy. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
Research highlights► Several nuclear receptors are highly expressed in the kidney. ► Animal studies using activating ligands, knockout mice, or transgenic mice have shown that FXR, VDR, and PPARs play an important role in modulation of kidney disease. ► Several human trials are essentially in agreement with the animal studies. ► Activation of VDR, FXR, and PPARs modulates kidney disease by regulating lipid metabolism, inflammation, oxidative stress, and fibrosis. ► There are several additional nuclear receptors whose function in the kidney remain unknown.