RT info:eu-repo/semantics/article
T1 Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
A1 Rámila Gutiérrez, David
A1 Ardura, Juan Antonio
A1 Esteban, Vanesa
A1 Ortega de Mues, Arantxa
A1 Ruíz-Ortrega, Marta
A1 Bosch Martínez, Ricardo José
A1 Esbrit, Pedro
K1 Inflammation
K1 Mice
K1 Obstructive nephropathy
K1 PTHrP
K1 Renal tubuloepithelial cells
K1 Medicine
K1 Biology
K1 Biología
K1 Medicina
AB Parathyroid hormone-related protein (PTHrP) promotesfibrogenesis in the acutely damaged kidney. Consideringthe relation between fibrosis and inflammation, we studiedtransgenic mice that overexpress PTHrP in the proximaltubule. When unilateral ureteric obstruction was induced inthese transgenic mice, we found that they had more renaltubulointerstitial damage, leukocyte influx, and expressionof proinflammatory factors than their control littermates.Reversal of PTHrP constitutive overexpression in thesetransgenic mice or treatment of control mice with the PTHrPantagonist (7–34) decreased this inflammatory response.Losartan, which abolished obstruction-induced endogenousPTHrP upregulation, also decreased the latter responsebut less effectively in transgenic mice. The PTHrP fragment(1–36) induced nuclear factor-jB (NF-jB) activation andproinflammatory cytokine overexpression in mouse corticaltubule cells in culture as well as migration of the macrophagecell 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 roleof PTHrP in the renal inflammatory process that results fromureteral obstruction and indicate that ERK-mediated NF-jBactivation seems to be an important mechanism wherebyPTHrP triggers renal inflammation
SN 0085-2538
YR 2008
FD 2008-01-09
LK http://hdl.handle.net/10017/50410
UL http://hdl.handle.net/10017/50410
LA eng
DS MINDS@UW
RD 01-may-2024