Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter

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...

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Autores: Rámila Gutiérrez, David, Ardura, Juan Antonio, Esteban, Vanesa, Ortega de Mues, Arantxa, Ruiz Ortega, Marta, Bosch Martínez, Ricardo José|||0000-0002-9094-1204, Esbrit, Pedro
Tipo de recurso: artículo
Fecha de publicación:2008
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/50410
Acceso en línea:http://hdl.handle.net/10017/50410
https://dx.doi.org/10.1038/sj.ki.5002775
Access Level:acceso abierto
Palabra clave:Inflammation
Mice
Obstructive nephropathy
PTHrP
Renal tubuloepithelial cells
Medicine
Biology
Biología
Medicina
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spelling Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureterRámila Gutiérrez, DavidArdura, Juan AntonioEsteban, VanesaOrtega de Mues, ArantxaRuiz Ortega, MartaBosch Martínez, Ricardo José|||0000-0002-9094-1204Esbrit, PedroInflammationMiceObstructive nephropathyPTHrPRenal tubuloepithelial cellsMedicineBiologyBiologíaMedicinaParathyroid 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 inflammation20082008-01-09journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/50410https://dx.doi.org/10.1038/sj.ki.5002775reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/504102026-06-18T11:13:07Z
dc.title.none.fl_str_mv Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
title Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
spellingShingle Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
Rámila Gutiérrez, David
Inflammation
Mice
Obstructive nephropathy
PTHrP
Renal tubuloepithelial cells
Medicine
Biology
Biología
Medicina
title_short Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
title_full Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
title_fullStr Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
title_full_unstemmed Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
title_sort Parathyroid Hormone-Related Protein Promotes Inflammation in the kidney with an Obstructed ureter
dc.creator.none.fl_str_mv Rámila Gutiérrez, David
Ardura, Juan Antonio
Esteban, Vanesa
Ortega de Mues, Arantxa
Ruiz Ortega, Marta
Bosch Martínez, Ricardo José|||0000-0002-9094-1204
Esbrit, Pedro
author Rámila Gutiérrez, David
author_facet Rámila Gutiérrez, David
Ardura, Juan Antonio
Esteban, Vanesa
Ortega de Mues, Arantxa
Ruiz Ortega, Marta
Bosch Martínez, Ricardo José|||0000-0002-9094-1204
Esbrit, Pedro
author_role author
author2 Ardura, Juan Antonio
Esteban, Vanesa
Ortega de Mues, Arantxa
Ruiz Ortega, Marta
Bosch Martínez, Ricardo José|||0000-0002-9094-1204
Esbrit, Pedro
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Inflammation
Mice
Obstructive nephropathy
PTHrP
Renal tubuloepithelial cells
Medicine
Biology
Biología
Medicina
topic Inflammation
Mice
Obstructive nephropathy
PTHrP
Renal tubuloepithelial cells
Medicine
Biology
Biología
Medicina
description 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
publishDate 2008
dc.date.none.fl_str_mv 2008
2008-01-09
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/50410
https://dx.doi.org/10.1038/sj.ki.5002775
url http://hdl.handle.net/10017/50410
https://dx.doi.org/10.1038/sj.ki.5002775
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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