Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 304, Issue 6, Pages F788-F800Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00306.2012
Keywords
diabetes; nephropathy; apelin; inflammation
Categories
Funding
- JDRF [1-2010-141]
- Cancer Therapy and Research Center at the University of Texas Health Science Center, San Antonio, TX, through National Cancer Insitute Cancer Center [2 P30 CA-054174-17]
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Day RT, Cavaglieri RC, Feliers D. Apelin retards the progression of diabetic nephropathy. Am J Physiol Renal Physiol 304: F788-F800, 2013. First published January 9, 2012; doi:10.1152/ajprenal.00306.2012.-Apelin and its receptor APJ have pleiotropic effects in mice and humans and play a protective role in cardiovascular diseases at least partially by inhibiting oxidative stress. Our objective was to study the effect of apelin on the progression of kidney disease in mice with established type 1 diabetes. Ove26 mice with type 1 diabetes received daily subcutaneous injections of apelin for 2 or 14 wk. APJ localizes in the glomeruli and blood vessels of kidneys. Renal APJ expression was reduced in diabetic mice but increased after treatment with apelin. Apelin treatment did not affect glycemia, body weight, or blood pressure in diabetic mice. Whole kidney and glomerular hypertrophy, as well as renal inflammation, including monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression, NF-kappa B activation, and monocyte infiltration, was inhibited after short and long treatment with apelin. Apelin administration significantly reduced albuminuria at 6 mo. Short treatment with apelin was sufficient to reverse the downregulation of the antioxidant enzyme catalase. Expression of angiotensin II and angiotensin type 1 receptor (AT(1)) in kidneys from diabetic mice treated was not affected by apelin. These findings show for the first time that apelin exerts a protective effect on the diabetic kidney. Short administration is sufficient to reduce kidney and glomerular hypertrophy as well as renal inflammation, but prolonged treatment is required to improve albuminuria. This effect was independent of the activation of the renin angiotensin system but correlated with upregulation of the antioxidant catalase. Apelin may represent a novel tool to treat diabetic nephropathy.
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