The parathyroid hormone-related protein system and diabetic nephropathy outcome in mice with streptozotocin-induced diabetes
Authors
Izquierdo Lahuerta, Adriana; López Luna, Pilar; Ortega de Mues, Arantxa; Romero de Pablos, Montserrat; Gutiérrez-Tarrés, María Antonia; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/50399DOI: 10.1038/sj.ki.5000195
ISSN: 0085-2538
Date
2006-06-03Bibliographic citation
Kidney International, 2006, v. 69, p. 2171-2178
Keywords
Diabetic nephropathy
Diabetes mellitus
Parathyroid hormone-related protein
PTH1 receptor
Proteinuria
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
© 2006 International Society of Nephrology
Access rights
info:eu-repo/semantics/openAccess
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.
Files in this item
Files | Size | Format |
|
---|---|---|---|
parathyroid_izquierdo_KI_2006.pdf | 324.1Kb |
|
Files | Size | Format |
|
---|---|---|---|
parathyroid_izquierdo_KI_2006.pdf | 324.1Kb |
|
Collections
- FISIOLOG - Artículos [87]