Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia

Autores
Fussi, María Fernanda; Hidalgo, Florencia; Buono, Gabriel Marcelo; Marquez, Susana Beatriz; Pariani, Alejandro Pedro; Molinas, Jorge Luis; Larocca, Maria Cecilia; Monasterolo, Liliana Alicia; Molinas, Sara Maria
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
During ischemic acute kidney injury (AKI), loss of cytoskeletal integrity and disruption of intercellular junctions are rapid events in response to ATP depletion. Angiotensin II type 2 receptor (AT2R) is overexpressed in injury situations and its stimulation by angiotensin II (AngII) is related to beneficial renal effects. Its role on ischemic AKI has not been deeply studied. The aim of the present study was to investigate whether pretreatment with the AT2R agonist, C21, prevents ischemic renal epithelial cell injury. Studies in a model of 40 min of renal ischemia followed by 24 h of reperfusion (IR) in rats demonstrated that C21 pretreatment attenuated renal dysfunction and induced better preservation of tubular architecture. In addition, we studied the expression of Rho GTPases, RhoA and Cdc42, since they are key proteins in the regulation of the actin cytoskeleton and the stability of epithelial intercellular junctions. IR downregulated RhoA and Cdc42 abundance in rat kidneys. C21 pretreatment prevented RhoA reduction and increased Cdc42 abundance compared to controls. We also used an in vitro model of ATP depletion in MDCK cells grown on filter support. Using immunofluorescence we observed that in MDCK cells, C21 pretreatment prevented the ATP depletion-induced reduction of actin in brush border microvilli and in stress fibers. Moreover, C21 prevented membrane E-cadherin reduction, and RhoA and Cdc42 downregulation. The present study describes for the first time a renoprotective effect of the AT2R agonist, C21, against AKI, and provides evidence supporting that stimulation of AT2R triggers cytoprotective mechanisms against an ischemic event.
Fil: Fussi, María Fernanda. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Hidalgo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Buono, Gabriel Marcelo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Marquez, Susana Beatriz. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Fil: Pariani, Alejandro Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Molinas, Jorge Luis. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina
Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Monasterolo, Liliana Alicia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Molinas, Sara Maria. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Materia
ACUTE KIDNEY INJURY
ANGIOTENSIN II TYPE 2 RECEPTOR
COMPOUND 21
ISCHEMIA
TUBULAR EPITHELIAL CELL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/153561
Acceder
id CONICETDig_237a87444d5740476c4edf92f14eceb5
oai_identifier_str oai:ri.conicet.gov.ar:11336/153561
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemiaFussi, María FernandaHidalgo, FlorenciaBuono, Gabriel MarceloMarquez, Susana BeatrizPariani, Alejandro PedroMolinas, Jorge LuisLarocca, Maria CeciliaMonasterolo, Liliana AliciaMolinas, Sara MariaACUTE KIDNEY INJURYANGIOTENSIN II TYPE 2 RECEPTORCOMPOUND 21ISCHEMIATUBULAR EPITHELIAL CELLhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3During ischemic acute kidney injury (AKI), loss of cytoskeletal integrity and disruption of intercellular junctions are rapid events in response to ATP depletion. Angiotensin II type 2 receptor (AT2R) is overexpressed in injury situations and its stimulation by angiotensin II (AngII) is related to beneficial renal effects. Its role on ischemic AKI has not been deeply studied. The aim of the present study was to investigate whether pretreatment with the AT2R agonist, C21, prevents ischemic renal epithelial cell injury. Studies in a model of 40 min of renal ischemia followed by 24 h of reperfusion (IR) in rats demonstrated that C21 pretreatment attenuated renal dysfunction and induced better preservation of tubular architecture. In addition, we studied the expression of Rho GTPases, RhoA and Cdc42, since they are key proteins in the regulation of the actin cytoskeleton and the stability of epithelial intercellular junctions. IR downregulated RhoA and Cdc42 abundance in rat kidneys. C21 pretreatment prevented RhoA reduction and increased Cdc42 abundance compared to controls. We also used an in vitro model of ATP depletion in MDCK cells grown on filter support. Using immunofluorescence we observed that in MDCK cells, C21 pretreatment prevented the ATP depletion-induced reduction of actin in brush border microvilli and in stress fibers. Moreover, C21 prevented membrane E-cadherin reduction, and RhoA and Cdc42 downregulation. The present study describes for the first time a renoprotective effect of the AT2R agonist, C21, against AKI, and provides evidence supporting that stimulation of AT2R triggers cytoprotective mechanisms against an ischemic event.Fil: Fussi, María Fernanda. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; ArgentinaFil: Hidalgo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Buono, Gabriel Marcelo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; ArgentinaFil: Marquez, Susana Beatriz. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Pariani, Alejandro Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Molinas, Jorge Luis. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; ArgentinaFil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Monasterolo, Liliana Alicia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Molinas, Sara Maria. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaPergamon-Elsevier Science Ltd2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153561Fussi, María Fernanda; Hidalgo, Florencia; Buono, Gabriel Marcelo; Marquez, Susana Beatriz; Pariani, Alejandro Pedro; et al.; Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 194; 12-2021; 1-330006-29521873-2968CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006295221004202?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2021.114804info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:33Zoai:ri.conicet.gov.ar:11336/153561instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:34.003CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
title Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
spellingShingle Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
Fussi, María Fernanda
ACUTE KIDNEY INJURY
ANGIOTENSIN II TYPE 2 RECEPTOR
COMPOUND 21
ISCHEMIA
TUBULAR EPITHELIAL CELL
title_short Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
title_full Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
title_fullStr Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
title_full_unstemmed Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
title_sort Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia
dc.creator.none.fl_str_mv Fussi, María Fernanda
Hidalgo, Florencia
Buono, Gabriel Marcelo
Marquez, Susana Beatriz
Pariani, Alejandro Pedro
Molinas, Jorge Luis
Larocca, Maria Cecilia
Monasterolo, Liliana Alicia
Molinas, Sara Maria
author Fussi, María Fernanda
author_facet Fussi, María Fernanda
Hidalgo, Florencia
Buono, Gabriel Marcelo
Marquez, Susana Beatriz
Pariani, Alejandro Pedro
Molinas, Jorge Luis
Larocca, Maria Cecilia
Monasterolo, Liliana Alicia
Molinas, Sara Maria
author_role author
author2 Hidalgo, Florencia
Buono, Gabriel Marcelo
Marquez, Susana Beatriz
Pariani, Alejandro Pedro
Molinas, Jorge Luis
Larocca, Maria Cecilia
Monasterolo, Liliana Alicia
Molinas, Sara Maria
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACUTE KIDNEY INJURY
ANGIOTENSIN II TYPE 2 RECEPTOR
COMPOUND 21
ISCHEMIA
TUBULAR EPITHELIAL CELL
topic ACUTE KIDNEY INJURY
ANGIOTENSIN II TYPE 2 RECEPTOR
COMPOUND 21
ISCHEMIA
TUBULAR EPITHELIAL CELL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv During ischemic acute kidney injury (AKI), loss of cytoskeletal integrity and disruption of intercellular junctions are rapid events in response to ATP depletion. Angiotensin II type 2 receptor (AT2R) is overexpressed in injury situations and its stimulation by angiotensin II (AngII) is related to beneficial renal effects. Its role on ischemic AKI has not been deeply studied. The aim of the present study was to investigate whether pretreatment with the AT2R agonist, C21, prevents ischemic renal epithelial cell injury. Studies in a model of 40 min of renal ischemia followed by 24 h of reperfusion (IR) in rats demonstrated that C21 pretreatment attenuated renal dysfunction and induced better preservation of tubular architecture. In addition, we studied the expression of Rho GTPases, RhoA and Cdc42, since they are key proteins in the regulation of the actin cytoskeleton and the stability of epithelial intercellular junctions. IR downregulated RhoA and Cdc42 abundance in rat kidneys. C21 pretreatment prevented RhoA reduction and increased Cdc42 abundance compared to controls. We also used an in vitro model of ATP depletion in MDCK cells grown on filter support. Using immunofluorescence we observed that in MDCK cells, C21 pretreatment prevented the ATP depletion-induced reduction of actin in brush border microvilli and in stress fibers. Moreover, C21 prevented membrane E-cadherin reduction, and RhoA and Cdc42 downregulation. The present study describes for the first time a renoprotective effect of the AT2R agonist, C21, against AKI, and provides evidence supporting that stimulation of AT2R triggers cytoprotective mechanisms against an ischemic event.
Fil: Fussi, María Fernanda. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Hidalgo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Buono, Gabriel Marcelo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Marquez, Susana Beatriz. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina
Fil: Pariani, Alejandro Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Molinas, Jorge Luis. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina
Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Monasterolo, Liliana Alicia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Molinas, Sara Maria. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
description During ischemic acute kidney injury (AKI), loss of cytoskeletal integrity and disruption of intercellular junctions are rapid events in response to ATP depletion. Angiotensin II type 2 receptor (AT2R) is overexpressed in injury situations and its stimulation by angiotensin II (AngII) is related to beneficial renal effects. Its role on ischemic AKI has not been deeply studied. The aim of the present study was to investigate whether pretreatment with the AT2R agonist, C21, prevents ischemic renal epithelial cell injury. Studies in a model of 40 min of renal ischemia followed by 24 h of reperfusion (IR) in rats demonstrated that C21 pretreatment attenuated renal dysfunction and induced better preservation of tubular architecture. In addition, we studied the expression of Rho GTPases, RhoA and Cdc42, since they are key proteins in the regulation of the actin cytoskeleton and the stability of epithelial intercellular junctions. IR downregulated RhoA and Cdc42 abundance in rat kidneys. C21 pretreatment prevented RhoA reduction and increased Cdc42 abundance compared to controls. We also used an in vitro model of ATP depletion in MDCK cells grown on filter support. Using immunofluorescence we observed that in MDCK cells, C21 pretreatment prevented the ATP depletion-induced reduction of actin in brush border microvilli and in stress fibers. Moreover, C21 prevented membrane E-cadherin reduction, and RhoA and Cdc42 downregulation. The present study describes for the first time a renoprotective effect of the AT2R agonist, C21, against AKI, and provides evidence supporting that stimulation of AT2R triggers cytoprotective mechanisms against an ischemic event.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/153561
Fussi, María Fernanda; Hidalgo, Florencia; Buono, Gabriel Marcelo; Marquez, Susana Beatriz; Pariani, Alejandro Pedro; et al.; Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 194; 12-2021; 1-33
0006-2952
1873-2968
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153561
identifier_str_mv Fussi, María Fernanda; Hidalgo, Florencia; Buono, Gabriel Marcelo; Marquez, Susana Beatriz; Pariani, Alejandro Pedro; et al.; Angiotensin ii type 2 receptor agonist, compound 21, prevents tubular epithelial cell damage caused by renal ischemia; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 194; 12-2021; 1-33
0006-2952
1873-2968
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006295221004202?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2021.114804
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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