Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation

Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multif...

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Autores principales:	Heitrich, Mauro Oscar, García, Daiana María de los Ángeles, Stoyanoff, Tania Romina, Rodríguez, Juan Pablo, Todaro, Juan Santiago, Aguirre, María Victoria
Formato:	Artículo
Lenguaje:	Inglés
Publicado:	Elsevier 2022
Materias:	Cecal ligation and puncture (CLP) Sepsis Erythropoietin (EPO) Acute lung injury (ALI) Acute kidney injury (AKI)
Acceso en línea:	http://repositorio.unne.edu.ar/handle/123456789/47782
Aporte de:	RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE) de Universidad Nacional del Nordeste

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spelling	I48-R184-123456789-477822024-12-16T11:36:01Z Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation Heitrich, Mauro Oscar García, Daiana María de los Ángeles Stoyanoff, Tania Romina Rodríguez, Juan Pablo Todaro, Juan Santiago Aguirre, María Victoria Cecal ligation and puncture (CLP) Sepsis Erythropoietin (EPO) Acute lung injury (ALI) Acute kidney injury (AKI) Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis. Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP + EPO (3000 IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18 h post-surgery. Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2. Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality. This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLPinduced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair. 2022-05-19T14:40:09Z 2022-05-19T14:40:09Z 2016 Artículo Heitrich, Mauro, et al., 2016. Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation. Biomedicine & Pharmacotherapy. Ámsterdam: Elsevier, vol. 82, p. 603-616. ISSN 0753-3322. 0753-3322 http://repositorio.unne.edu.ar/handle/123456789/47782 eng openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf Elsevier Biomedicine & Pharmacotherapy, 2016, vol. 38, p. 603-616.
institution	Universidad Nacional del Nordeste
institution_str	I-48
repository_str	R-184
collection	RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE)
language	Inglés
topic	Cecal ligation and puncture (CLP) Sepsis Erythropoietin (EPO) Acute lung injury (ALI) Acute kidney injury (AKI)
spellingShingle	Cecal ligation and puncture (CLP) Sepsis Erythropoietin (EPO) Acute lung injury (ALI) Acute kidney injury (AKI) Heitrich, Mauro Oscar García, Daiana María de los Ángeles Stoyanoff, Tania Romina Rodríguez, Juan Pablo Todaro, Juan Santiago Aguirre, María Victoria Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation
topic_facet	Cecal ligation and puncture (CLP) Sepsis Erythropoietin (EPO) Acute lung injury (ALI) Acute kidney injury (AKI)
description	Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis. Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP + EPO (3000 IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18 h post-surgery. Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2. Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality. This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLPinduced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair.
format	Artículo
author	Heitrich, Mauro Oscar García, Daiana María de los Ángeles Stoyanoff, Tania Romina Rodríguez, Juan Pablo Todaro, Juan Santiago Aguirre, María Victoria
author_facet	Heitrich, Mauro Oscar García, Daiana María de los Ángeles Stoyanoff, Tania Romina Rodríguez, Juan Pablo Todaro, Juan Santiago Aguirre, María Victoria
author_sort	Heitrich, Mauro Oscar
title	Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation
title_short	Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation
title_full	Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation
title_fullStr	Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation
title_full_unstemmed	Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation
title_sort	erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through epo-r, vegf and vegf-r2 modulation
publisher	Elsevier
publishDate	2022
url	http://repositorio.unne.edu.ar/handle/123456789/47782
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Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation

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