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

Jessica R. Mader, Zachary T. Resch, Gary R. McLean, Jakob H. Mikkelsen, Claus Oxvig, Ronald J. Marler, Cheryl A. Conover

Research output: Contribution to journalArticle

18 Scopus citations

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 in14-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, elevatedPAPP-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 diabeticnephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalJournal of Endocrinology
Volume219
Issue number1
DOIs
StatePublished - 2013

Keywords

  • Bowman's capsule
  • Diabetes
  • Kidney
  • Pregnancy-associated plasma protein-A

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Mader, J. R., Resch, Z. T., McLean, G. R., Mikkelsen, J. H., Oxvig, C., Marler, R. J., & Conover, C. A. (2013). Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy. Journal of Endocrinology, 219(1), 51-58. https://doi.org/10.1530/JOE-13-0167