Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice

Kumar Sharma, Lewei Wang, Yanqing Zhu, Aurora Deguzman, Gao Yuan Cao, Richard B. Lynn, Suresh K. Joseph

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The mechanisms underlying glomerular hypertrophy and hyperfiltration in diabetes remain unclear. We have previously demonstrated that the cytokine transforming growth factor-β1 (TGF-β1) is increased in early diabetic kidney disease and TGF-β1 inhibits the expression of the inositol 1,4,5- trisphosphate (IP3)-gated calcium channel, the type I IP3 receptor (IP3R), in mesangial cells. To test the hypothesis that reduced type I IP3R may be important in diabetic kidney disease, we evaluated type I IP3R expression in the kidney of streptozotocin-induced diabetic rats and mice. Two-week-old diabetic rats have decreased renal type I IP3R protein and mRNA levels. Immunostaining of normal rat kidney demonstrated presence of type I IP3R in glomerular and vascular smooth muscle cells, whereas diabetic rats had reduced staining in both compartments. Reduction of type I IP3R also occurred in parallel with renal hypertrophy, increased creatinine clearance, and increased renal TGF-β1 expression in the diabetic rats. Two-week-old diabetic mice also had reduced renal type I IP3R protein and mRNA expression in association with renal hypertrophy and increased TGF-β1 mRNA expression. These findings demonstrate that there is reduced type I IP3R in glomerular and vascular smooth muscle cells in the diabetic kidney, which may contribute to the altered renal vasoregulation and renal hypertrophy of diabetes.

Original languageEnglish (US)
Pages (from-to)F54-F61
JournalAmerican Journal of Physiology - Renal Physiology
Volume276
Issue number1 45-1
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Diabetic renal hypertrophy
  • Hyperfiltration
  • Inositol 1,4,5-trisphosphate receptor
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Urology

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