Upstream regulators and downstream effectors of NADPH oxidases as novel therapeutic targets for diabetic kidney disease

Mol Cells. 2015 Apr;38(4):285-96. doi: 10.14348/molcells.2015.0010. Epub 2015 Mar 31.


Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-β. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

Keywords: Nox family of NADPH oxidases; diabetic nephropathy; downstream effectors of Nox NADPH oxidases; oxidative stress; upstream regulators of Nox NADPH oxidases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Humans
  • Molecular Targeted Therapy
  • NADPH Oxidases / metabolism*
  • Oxidative Stress
  • Signal Transduction


  • NADPH Oxidases