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J Am Soc Nephrol. 2015 Oct;26(10):2447-59. doi: 10.1681/ASN.2014060613. Epub 2015 Feb 2.

Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease.

Author information

1
Departments of Medicine and.
2
Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
3
Division of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
4
Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Division of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China liuy@upmc.edu.

Abstract

Extracellular superoxide dismutase (EC-SOD), also known as SOD3, is an antioxidant expressed at high levels in normal adult kidneys. Because oxidative stress contributes to a variety of kidney injuries, we hypothesized that EC-SOD may be protective in CKD progression. To study this hypothesis, we used a murine model of ADR nephropathy characterized by albuminuria and renal dysfunction. We found that levels of EC-SOD diminished throughout the course of disease progression and were associated with increased levels of NADPH oxidase and oxidative stress markers. EC-SOD null mice were sensitized to ADR injury, as evidenced by increases in albuminuria, serum creatinine, histologic damage, and oxidative stress. The absence of EC-SOD led to increased levels of NADPH oxidase and an increase in β-catenin signaling, which has been shown to be pathologic in a variety of kidney injuries. Exposure of EC-SOD null mice to either chronic angiotensin II infusion or to daily albumin injections also caused increased proteinuria. In contrast, EC-SOD null mice subjected to nonproteinuric CKD induced by unilateral ureteral obstruction exhibited no differences compared with wild-type mice. Finally, we also found a decrease in EC-SOD in human CKD biopsy samples, similar to our findings in mice. Therefore, we conclude that EC-SOD is protective in CKDs characterized by proteinuria.

KEYWORDS:

kidney disease; oxidative stress; podocyte; proteinuria

PMID:
25644107
PMCID:
PMC4587687
DOI:
10.1681/ASN.2014060613
[Indexed for MEDLINE]
Free PMC Article

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