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Review
, 38 (4), 285-96

Upstream Regulators and Downstream Effectors of NADPH Oxidases as Novel Therapeutic Targets for Diabetic Kidney Disease

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Review

Upstream Regulators and Downstream Effectors of NADPH Oxidases as Novel Therapeutic Targets for Diabetic Kidney Disease

Yves Gorin et al. Mol Cells.

Abstract

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.

Figures

Fig. 1.
Fig. 1.
Structure and molecular organization of the renal Nox NADPH oxidases. The top right left panel illustrates the topology of and the enzymatic reaction catalyzed by the Nox enzymes. The other panels represent the molecular structure of the Nox oxidase homologues predominantly expressed in the kidney, Nox2 (a.k.a. gp91phox), Nox1, Nox4, and Nox5. The regulatory subunits differ from a Nox homologue to another.
Fig. 2.
Fig. 2.
Upstream and downstream effectors of Nox oxidases implicated in glomerular mesangial cell injury triggered by diabetic stimuli. See text for detail.
Fig. 3.
Fig. 3.
Upstream and downstream effectors of Nox oxidases implicated in podocyte injury triggered by diabetic stimuli. See text for detail.
Fig. 4.
Fig. 4.
Upstream and downstream effectors of Nox oxidases implicated in tubular cell injury triggered by diabetic stimuli. See text for detail.

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References

    1. Abboud H.E. Growth factors and diabetic nephrology: an overview. Kidney Int. 1997;60(Supplement):S3–6. - PubMed
    1. Ago T., Kuroda J., Pain J., Fu C., Li H., Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ. Res. 2010;106:1253–1264. - PMC - PubMed
    1. Altenhofer S., Kleikers P.W., Radermacher K.A., Scheurer P., Rob Hermans J.J., Schiffers P., Ho H., Wingler K., Schmidt H.H. The NOX toolbox: validating the role of NADPH oxidases in physiology and disease. Cell. Mol. Life Sci. 2012;69:2327–2343. - PMC - PubMed
    1. Aoyama T., Paik Y.H., Watanabe S., Laleu B., Gaggini F., Fioraso-Cartier L., Molango S., Heitz F., Merlot C., Szyndralewiez C., et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology. 2012;56:2316–2327. - PMC - PubMed
    1. Asaba K., Tojo A., Onozato M.L., Goto A., Quinn M.T., Fujita T., Wilcox C.S. Effects of NADPH oxidase inhibitor in diabetic nephropathy. Kidney Int. 2005;67:1890–1898. - PubMed

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