Role of Nox2 in diabetic kidney disease.
Authors You YH, Okada S, Ly S, Jandeleit-Dahm K, Barit D, Namikoshi T, Sharma K
Submitted By Kumar Sharma on 7/10/2013
Status Published
Journal American journal of physiology. Renal physiology
Year 2013
Date Published 4/1/2013
Volume : Pages 304 : F840 - F848
PubMed Reference 23389458
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-ß) 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.

Investigators with authorship
Kumar SharmaUniversity of California San Diego