کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3890034 1249690 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes
چکیده انگلیسی

The pathophysiology of the diabetic kidney (e.g., hypertrophy, increased urinary albumin excretion (UAE)) is still ill-defined. Parathyroid hormone-related protein (PTHrP) is overexpressed in several nephropathies, but its role remains unclear. We evaluated the effect of high glucose on PTHrP and the PTH1 receptor (PTH1R) protein (by Western blot and immunohistochemistry) in the kidney of mice with streptozotocin-induced diabetes, and in several mouse renal cells in vitro. Diabetic mice showed a significantly increased renal expression of PTHrP and PTH1R proteins within 2–8 weeks from the onset of diabetes. These animals exhibited an intense immunostaining for both proteins in the renal tubules and glomeruli. Using transgenic mice overexpressing PTHrP targeted to the renal proximal tubule, we found a significant increase in the renal hypertrophy index and in UAE in these diabetic mice relative to their control littermates. Moreover, logistic regression analysis showed a significant association between both PTHrP and PTH1R protein levels and UAE in all diabetic mice throughout the study. High-glucose (25 mM) medium was found to increase PTHrP and PTH1R in tubuloepithelial cells, mesangial cells, and podocytes in vitro. Moreover, this increase in PTHrP (but not that of PTH1R) was inhibited by the AT1 receptor antagonist losartan. Collectively, these results indicate that the renal PTHrP/PTH1R system is upregulated in streptozotozin-induced diabetes in mice, and appears to adversely affect the outcome of diabetic renal disease. Our findings also suggest that angiotensin II might have a role in the PTHrP upregulation in this condition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 69, Issue 12, 2 June 2006, Pages 2171–2178
نویسندگان
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