Mice deficient in PAPP - a show resistance to the development of diabetic nephropathy

Mader, Jessica R. and Resch, Zachary T. and McLean, Gary R. and Mikkelsen, Jakob H. and Oxvig, Claus and Marler, Ronald J. and Conover, Cheryl A. (2013) Mice deficient in PAPP - a show resistance to the development of diabetic nephropathy. The Journal of endocrinology, 219 (1). pp. 51-8. ISSN 1479-6805

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Abstract

We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

Item Type: Article
Uncontrolled Keywords: pregnancy-associated plasma protein-A, kidney, diabetes, Bowman’s capsule
Subjects: 600 Technology > 610 Medicine & health
Department: School of Human Sciences
Depositing User: Gary Mclean
Date Deposited: 17 Jul 2015 07:56
Last Modified: 17 Jul 2015 07:56
URI: http://repository.londonmet.ac.uk/id/eprint/652

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