TITLE

The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes

AUTHOR(S)
Izquierdo, A.; López-Luna, P.; Ortega, A.; Romero, M.; Gutiérrez-Tarrés, M. A.; Arribas, I.; Álvarez, M. J. R.; Esbrit, P.; Bosch, R. J.
PUB. DATE
June 2006
SOURCE
Kidney International;Jun2006, Vol. 69 Issue 12, p2171
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.Kidney International (2006) 69, 2171–2178. doi:10.1038/sj.ki.5000195; published online 3 May 2006
ACCESSION #
21091109

 

Related Articles

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics