%0 Journal Article 
%A Rámila Gutiérrez, David
%A Ardura, Juan Antonio
%A Esteban, Vanesa
%A Ortega de Mues, Arantxa
%A Ruíz-Ortrega, Marta
%A Bosch Martínez, Ricardo José
%A Esbrit, Pedro
%T Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
%D 2008
%@ 0085-2538
%U http://hdl.handle.net/10017/50410
%X Parathyroid hormone-related protein (PTHrP) promotes
fibrogenesis in the acutely damaged kidney. Considering
the relation between fibrosis and inflammation, we studied
transgenic mice that overexpress PTHrP in the proximal
tubule. When unilateral ureteric obstruction was induced in
these transgenic mice, we found that they had more renal
tubulointerstitial damage, leukocyte influx, and expression
of proinflammatory factors than their control littermates.
Reversal of PTHrP constitutive overexpression in these
transgenic mice or treatment of control mice with the PTHrP
antagonist (7–34) decreased this inflammatory response.
Losartan, which abolished obstruction-induced endogenous
PTHrP upregulation, also decreased the latter response
but less effectively in transgenic mice. The PTHrP fragment
(1–36) induced nuclear factor-jB (NF-jB) activation and
proinflammatory cytokine overexpression in mouse cortical
tubule cells in culture as well as migration of the macrophage
cell line Raw 264.7. All these effects were decreased by PTHrP
(7–34) and NF-jB or extracellular signal-regulated kinase
(ERK) activation inhibitors. Our findings suggest a critical role
of PTHrP in the renal inflammatory process that results from
ureteral obstruction and indicate that ERK-mediated NF-jB
activation seems to be an important mechanism whereby
PTHrP triggers renal inflammation
%K Inflammation
%K Mice
%K Obstructive nephropathy
%K PTHrP
%K Renal tubuloepithelial cells
%K Medicine
%K Biology
%K Biología
%K Medicina
%~ Biblioteca Universidad de Alcala