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dc.contributor.authorRodríguez Peña, Ana B.
dc.contributor.authorFuentes Calvo, Isabel
dc.contributor.authorDocherty, Neil G.
dc.contributor.authorArévalo, Miguel
dc.contributor.authorMª Teresa, Grande
dc.contributor.authorEleno, Nélida
dc.contributor.authorPérez Barriocanal, Fernando
dc.contributor.authorLópez Novoa, José Mª
dc.date.accessioned2019-10-31T12:20:27Z
dc.date.available2019-10-31T12:20:27Z
dc.date.issued2014
dc.identifier.issn2314-6133spa
dc.identifier.urihttp://hdl.handle.net10641/1708
dc.description.abstractTubulointerstitial 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 α-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 system and 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.spa
dc.language.isoengspa
dc.publisherBioMed Research Internationalspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.titleEffect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathyspa
dc.typearticlespa
dc.description.versionpost-printspa
dc.rights.accessRightsopenAccessspa
dc.description.extent2842 KBspa
dc.identifier.doi10.1155/2014/124902spa
dc.relation.publisherversionhttps://www.hindawi.com/journals/bmri/2014/124902/spa


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