Maternal diabetes programs hypertension and kidney injury in offspring

Yun-Wen Chen, Isabelle Chenier, Stella Tran, Michael Scotcher, Shiao Ying Chang, Shao Ling Zhang

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

We investigated whether maternal diabetes programs the offspring to develop hypertension and kidney injury in adulthood and examined potential underlying mechanisms. In a murine model we studied the offspring of three groups of dams (non-diabetic, diabetic, and diabetic treated with insulin). Mean systolic blood pressure in the offspring was monitored from 8 to 20 weeks. Body and kidney weights in the offspring of diabetic mothers were significantly lower than in offspring of non-diabetic mothers. Offspring of diabetic mothers developed hypertension, microalbuminuria, and glucose intolerance. Increased accumulation of extracellular matrix proteins in the glomeruli and marked upregulation of angiotensinogen, angiotensin II type 1 receptor, angiotensinconverting enzyme, transforming growth factor beta-1 (TGF-ß1), and plasminogen activator inhibitor-1 (PAI-1) gene expression were evident in the renal cortex of hypertensive offspring of diabetic mothers. By contrast, angiotensinconverting enzyme-2 (ACE2) gene expression was lower in the hypertensive offspring of diabetic mothers than in that of non-diabetic mothers. These changes were prevented in the offspring of insulin-treated diabetic mothers. These data indicate that maternal diabetes induces perinatal programming of hypertension, renal injury, and glucose intolerance in the offspring and suggest a central role for the activation of the intrarenal renin-angiotensin system and TGF-ß1 gene expression in this process.

Original languageEnglish
Pages (from-to)1319-1329
Number of pages11
JournalPediatric Nephrology
Volume25
Issue number7
DOIs
Publication statusPublished - 2010 Jul 1

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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