4.2 Review

Nox-4 and progressive kidney disease

Journal

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
Volume 24, Issue 1, Pages 74-80

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNH.0000000000000082

Keywords

diabetic nephropathy; NADPH oxidase; protein kinase C; reactive oxygen species

Funding

  1. Advanced Postdoctoral JDRF Fellowship [10-2012-227]
  2. JDRF [4-2010-52]
  3. Genkyotex Inc.

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Purpose of review Nox-4 is a member of the NADPH oxidase (Nox) family of enzymes implicated in reactive oxygen species generation. Nox-4 is distributed in many tissues; however, its physiological functions remain poorly understood. In contrast to other Nox isoforms, it is unique in that it produces large amounts of hydrogen peroxide constitutively and does not require other cytosolic oxidase components for its activation. This review highlights the recent developments in Nox-4 research and progressive kidney disease as well as the potential of new Nox-4 inhibitors to reduce renal damage. Recent findings Recently, Nox-4 was shown to be implicated in kidney diseases such as diabetic nephropathy. Nox-4 has been identified as playing a role in damage to the kidney induced by hyperglycaemia and other major pathways of renal damage, including advanced glycation end-products, the renin-angiotensin system, TGF-beta and protein kinase C. Summary The role of Nox-4 as a target for renoprotection remains controversial, although recent positive preclinical data have stimulated increased interest in inhibiting the enzyme in clinical trials of renal disease.

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