title: Role of Nox2 in diabetic kidney disease.
abstract: NADPH oxidase (Nox) isoforms have been implicated in contributing to diabetic microvascular complications, but the functional role of individual isoforms in diabetic kidney are unclear. Nox2, in particular, is highly expressed in phagocytes and may play a key inflammatory role in diabetic kidney disease. To determine the role of Nox2, we evaluated kidney function and pathology in wild-type (WT; C57BL/6) and Nox2 knockout (KO) mice with type 1 diabetes. Diabetes was induced in male Nox2 KO and WT mice with a multiple low-dose streptozotocin protocol. Groups were studied for kidney disease after 8 and 20 wk of diabetes. Hyperglycemia and body weights were similar in WT and Nox2 KO diabetic mice. All functional and structural features of early and later stage diabetic kidney disease (albuminuria, mesangial matrix, tubulointerstitial disease, and gene expression of matrix and transforming growth factor-β) were similar in both diabetic groups compared with their respective nondiabetic groups, except for reduction of macrophage infiltration and monocyte chemoattractant protein-1 in the diabetic Nox2 KO mice. Systolic blood pressure by telemetry was surprisingly increased in Nox2 KO mice; however, the systolic blood pressure was reduced in the diabetic WT and Nox2 KO mice by tail-cuff. Interestingly, diabetic Nox2 KO mice had marked upregulation of renal Nox4 at both the glomerular and cortical levels. The present results demonstrate that lack of Nox2 does not protect against diabetic kidney disease in type 1 diabetes, despite a reduction in macrophage infiltration. The lack of renoprotection may be due to upregulation of renal Nox4.
authors: Center for Renal Translational Medicine, Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Young-Hyun
authors: YH
authors: You
authors: Shinichi
authors: S
authors: Okada
authors: San
authors: S
authors: Ly
authors: Karin
authors: K
authors: Jandeleit-Dahm
authors: David
authors: D
authors: Barit
authors: Tamehachi
authors: T
authors: Namikoshi
authors: Kumar
authors: K
authors: Sharma
mesh_terms: D000419:Albuminuria / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000096:biosynthesis; D024141:Collagen Type IV / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology*; D005353:Fibronectins / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024141:Collagen Type IV; D005353:Fibronectins; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases
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