Role of Nox2 in diabetic kidney disease

Young Hyun You, Shinichi Okada, San Ly, Karin Jandeleit-Dahm, David Barit, Tamehachi Namikoshi, Kumar Sharma

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)F840-F848
JournalAmerican Journal of Physiology - Renal Physiology
Volume304
Issue number7
DOIs
StatePublished - 2013

Keywords

  • Albuminuria
  • Matrix
  • NADPH oxidase
  • Nephropathy
  • Nox2
  • Nox4
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Urology

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