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Nuclear hormone receptors in diabetic nephropathy

Abstract

Diabetes is the leading cause of end-stage renal disease in developed countries. In spite of glucose and blood pressure control, for example by use of angiotensin II receptor blockers, diabetic nephropathy still develops and progresses in affected patients and the development of additional protective therapeutic interventions is, therefore, required. Nuclear hormone receptors are transcription factors that 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 a host of 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. Eight nuclear receptors have shown a renoprotective effect in the context of diabetic nephropathy. This Review discusses the evidence regarding the beneficial effects of the activation of these receptors in preventing the progression of diabetic nephropathy and describes 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.

Key Points

  • Nuclear hormone receptor activity is abnormal in the diabetic kidney

  • Nuclear hormone receptors regulate metabolism, inflammation, oxidative stress and fibrosis

  • Modulation of the activity of the peroxisome-proliferator-associated receptor, vitamin D receptor, farnesoid X receptor and estrogen receptor holds great promise in the treatment of diabetic nephropathy

  • Further evidence on the role of nuclear hormone receptors in the diabetic kidney and the identification of additional specific ligands of these receptors will probably result in development of additional therapeutic strategies for diabetic nephropathy

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Figure 1: Nuclear hormone receptors in diabetic nephropathy.

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Correspondence to Moshe Levi.

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Wang, X., Jiang, T. & Levi, M. Nuclear hormone receptors in diabetic nephropathy. Nat Rev Nephrol 6, 342–351 (2010). https://doi.org/10.1038/nrneph.2010.56

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