Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

[EN] Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose o...

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Autores: Rodríguez-Peña, Ana B., Fuentes Calvo, Isabel, Docherty, Neil G., Arévalo Gómez, Miguel Ángel, Grande Rodríguez, María Teresa, Eleno Balboa, María Nélida, Pérez Barriocanal, Fernando, López-Novoa, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/140710
Acceso en línea:http://hdl.handle.net/10366/140710
Access Level:acceso abierto
Palabra clave:Obstructive Nephropathy
Small GTPase
Tubulointerstitial fibrosis
Unilateral ureteral obstruction (UUO)
Nefropatía obstructiva
Fibrosis tubulointersticial
Obstrucción ureteral unilateral (UUO)
Chronic Disease
Fibrosis
3209 Farmacología
3205.06 Nefrología
fibrosis
enfermedad crónica
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oai_identifier_str oai:gredos.usal.es:10366/140710
network_acronym_str ES
network_name_str España
repository_id_str
spelling Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive NephropathyRodríguez-Peña, Ana B.Fuentes Calvo, IsabelDocherty, Neil G.Arévalo Gómez, Miguel ÁngelGrande Rodríguez, María TeresaEleno Balboa, María NélidaPérez Barriocanal, FernandoLópez-Novoa, José M.Obstructive NephropathySmall GTPaseTubulointerstitial fibrosisUnilateral ureteral obstruction (UUO)Nefropatía obstructivaFibrosis tubulointersticialObstrucción ureteral unilateral (UUO)Chronic DiseaseFibrosis3209 Farmacología3205.06 Nefrologíafibrosisenfermedad crónica[EN] Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and -smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling systemand decreased the early fibrotic response in the obstructed kidney.This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.Hindawi Publishing Corporation (London, United Kingdom)202020202014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10366/140710reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1407102026-06-07T06:28:51Z
dc.title.none.fl_str_mv Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
title Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
spellingShingle Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
Rodríguez-Peña, Ana B.
Obstructive Nephropathy
Small GTPase
Tubulointerstitial fibrosis
Unilateral ureteral obstruction (UUO)
Nefropatía obstructiva
Fibrosis tubulointersticial
Obstrucción ureteral unilateral (UUO)
Chronic Disease
Fibrosis
3209 Farmacología
3205.06 Nefrología
fibrosis
enfermedad crónica
title_short Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
title_full Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
title_fullStr Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
title_full_unstemmed Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
title_sort Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy
dc.creator.none.fl_str_mv Rodríguez-Peña, Ana B.
Fuentes Calvo, Isabel
Docherty, Neil G.
Arévalo Gómez, Miguel Ángel
Grande Rodríguez, María Teresa
Eleno Balboa, María Nélida
Pérez Barriocanal, Fernando
López-Novoa, José M.
author Rodríguez-Peña, Ana B.
author_facet Rodríguez-Peña, Ana B.
Fuentes Calvo, Isabel
Docherty, Neil G.
Arévalo Gómez, Miguel Ángel
Grande Rodríguez, María Teresa
Eleno Balboa, María Nélida
Pérez Barriocanal, Fernando
López-Novoa, José M.
author_role author
author2 Fuentes Calvo, Isabel
Docherty, Neil G.
Arévalo Gómez, Miguel Ángel
Grande Rodríguez, María Teresa
Eleno Balboa, María Nélida
Pérez Barriocanal, Fernando
López-Novoa, José M.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Obstructive Nephropathy
Small GTPase
Tubulointerstitial fibrosis
Unilateral ureteral obstruction (UUO)
Nefropatía obstructiva
Fibrosis tubulointersticial
Obstrucción ureteral unilateral (UUO)
Chronic Disease
Fibrosis
3209 Farmacología
3205.06 Nefrología
fibrosis
enfermedad crónica
topic Obstructive Nephropathy
Small GTPase
Tubulointerstitial fibrosis
Unilateral ureteral obstruction (UUO)
Nefropatía obstructiva
Fibrosis tubulointersticial
Obstrucción ureteral unilateral (UUO)
Chronic Disease
Fibrosis
3209 Farmacología
3205.06 Nefrología
fibrosis
enfermedad crónica
description [EN] Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and -smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling systemand decreased the early fibrotic response in the obstructed kidney.This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.
publishDate 2014
dc.date.none.fl_str_mv 2014
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/140710
url http://hdl.handle.net/10366/140710
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Hindawi Publishing Corporation (London, United Kingdom)
publisher.none.fl_str_mv Hindawi Publishing Corporation (London, United Kingdom)
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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