Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice
| Autor: | Aurora DeGuzman, Richard B. Lynn, Yanqing Zhu, Suresh K. Joseph, Gao-Yuan Cao, Lewei Wang, Kumar Sharma |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Physiology medicine.medical_treatment Receptors Cytoplasmic and Nuclear Biology Kidney Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Mice Reference Values Transforming Growth Factor beta Internal medicine Diabetes mellitus medicine Animals Inositol 1 4 5-Trisphosphate Receptors Inositol Tissue Distribution Inositol phosphate Receptor chemistry.chemical_classification Glomerular Hypertrophy medicine.disease Streptozotocin Blotting Northern Rats Mice Inbred C57BL medicine.anatomical_structure Cytokine Endocrinology chemistry Calcium Channels medicine.drug |
| Zdroj: | The American journal of physiology. 276(1) |
| ISSN: | 0002-9513 |
| Popis: | 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 IP3receptor (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. |
| Databáze: | OpenAIRE |
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