Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy

Autores
García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Benardon, María Eugenia; Oliveros, Liliana Beatriz; Cuello Carrión, Fernando Darío; Gil Lorenzo, Andrea Fernanda; Manucha, Walter Ariel Fernando; Garramuño, Patricia
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Evidence suggesting that statins may contribute to renoprotection has been provided in experimental 28 and clinical studies. Statins restore endothelial nitric oxide (NO) levels by mechanisms including up-reg- 29 ulation of endothelial NO synthase (eNOS) expression. Caveolin-1/eNOS interaction is essential prevent- 30 ing inadequate NO levels. Here, we evaluated whether caveolin-1 associated with eNOS/Hsp70 31 expression may be involved in the mechanism by which rosuvastatin exerts tubulointerstitial fibrosis 32 protection in neonatal unilateral ureteral obstruction (UUO). Neonatal rats subjected to UUO within 33 2 days of birth and controls were treated daily with vehicle or rosuvastatin (10 mg/kg/day) by oral gavage 34 for 14 days. 35 After UUO, morphometric evaluation of interstitial fibrosis showed increased interstitial volume (Vv) 36 associated with reduced NO availability, increased mRNA and protein caveolin-1 expression as well as 37 downregulation eNOS and heat shock protein 70 (Hsp70) expression. Conversely, rosuvastatin treatment 38 attenuated the fibrotic response linked to high NO availability, decreased mRNA and protein caveolin-1 39 expression, and marked upregulation of eNOS and Hsp70 expression at transcriptional and posttranscrip- 40 tional levels. Moreover, protein?protein interactions determined by immunoprecipitation and by immu- 41 nofluorescence co-localization have shown decreased caveolin-1/eNOS as well as increased Hsp70/eNOS 42 interaction, after rosuvastatin treatment. A dose dependent effect of rosuvastatin on decreased caveolin-1 43 expression was shown in control cortex. 44 In conclusion, our data suggest that statins contribute to the protection against tubulointerstitial fibro- 45 sis injury in neonatal early kidney obstruction by increased NO availability, involving interaction of up- 46 regulated eNOS/Hsp70 and down-regulated caveolin-1.
Fil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Fil: Oliveros, Liliana Beatriz. Universidad Nacional de San Luis; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Fil: Garramuño, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Materia
CAVEOLIN-1
eNOS
HSP70
FIBROSIS
ROSUVASTATIN
OBSTRUCTIVE NEPHROPATHY
NITRIC OXIDE
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:11336/270604
Acceder
id CONICETDig_6bd75fb70ceedf87408dce1315b2b3ee
oai_identifier_str oai:ri.conicet.gov.ar:11336/270604
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathyGarcía, Isabel MercedesMazzei, Luciana JorgelinaBenardon, María EugeniaOliveros, Liliana BeatrizCuello Carrión, Fernando DaríoGil Lorenzo, Andrea FernandaManucha, Walter Ariel FernandoGarramuño, PatriciaCAVEOLIN-1eNOSHSP70FIBROSISROSUVASTATINOBSTRUCTIVE NEPHROPATHYNITRIC OXIDEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Evidence suggesting that statins may contribute to renoprotection has been provided in experimental 28 and clinical studies. Statins restore endothelial nitric oxide (NO) levels by mechanisms including up-reg- 29 ulation of endothelial NO synthase (eNOS) expression. Caveolin-1/eNOS interaction is essential prevent- 30 ing inadequate NO levels. Here, we evaluated whether caveolin-1 associated with eNOS/Hsp70 31 expression may be involved in the mechanism by which rosuvastatin exerts tubulointerstitial fibrosis 32 protection in neonatal unilateral ureteral obstruction (UUO). Neonatal rats subjected to UUO within 33 2 days of birth and controls were treated daily with vehicle or rosuvastatin (10 mg/kg/day) by oral gavage 34 for 14 days. 35 After UUO, morphometric evaluation of interstitial fibrosis showed increased interstitial volume (Vv) 36 associated with reduced NO availability, increased mRNA and protein caveolin-1 expression as well as 37 downregulation eNOS and heat shock protein 70 (Hsp70) expression. Conversely, rosuvastatin treatment 38 attenuated the fibrotic response linked to high NO availability, decreased mRNA and protein caveolin-1 39 expression, and marked upregulation of eNOS and Hsp70 expression at transcriptional and posttranscrip- 40 tional levels. Moreover, protein?protein interactions determined by immunoprecipitation and by immu- 41 nofluorescence co-localization have shown decreased caveolin-1/eNOS as well as increased Hsp70/eNOS 42 interaction, after rosuvastatin treatment. A dose dependent effect of rosuvastatin on decreased caveolin-1 43 expression was shown in control cortex. 44 In conclusion, our data suggest that statins contribute to the protection against tubulointerstitial fibro- 45 sis injury in neonatal early kidney obstruction by increased NO availability, involving interaction of up- 46 regulated eNOS/Hsp70 and down-regulated caveolin-1.Fil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaFil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; ArgentinaFil: Oliveros, Liliana Beatriz. Universidad Nacional de San Luis; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; ArgentinaFil: Garramuño, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; ArgentinaAcademic Press Inc Elsevier Science2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/270604García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Benardon, María Eugenia; Oliveros, Liliana Beatriz; Cuello Carrión, Fernando Darío; et al.; Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy; Academic Press Inc Elsevier Science; Nitric Oxide-Biology and Chemistry; 27; 2; 8-2012; 95-1051089-8603CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.niox.2012.05.006info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:21:04Zoai:ri.conicet.gov.ar:11336/270604instacron: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:34982025-10-15 14:21:04.455CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
title Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
spellingShingle Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
García, Isabel Mercedes
CAVEOLIN-1
eNOS
HSP70
FIBROSIS
ROSUVASTATIN
OBSTRUCTIVE NEPHROPATHY
NITRIC OXIDE
title_short Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
title_full Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
title_fullStr Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
title_full_unstemmed Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
title_sort Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy
dc.creator.none.fl_str_mv García, Isabel Mercedes
Mazzei, Luciana Jorgelina
Benardon, María Eugenia
Oliveros, Liliana Beatriz
Cuello Carrión, Fernando Darío
Gil Lorenzo, Andrea Fernanda
Manucha, Walter Ariel Fernando
Garramuño, Patricia
author García, Isabel Mercedes
author_facet García, Isabel Mercedes
Mazzei, Luciana Jorgelina
Benardon, María Eugenia
Oliveros, Liliana Beatriz
Cuello Carrión, Fernando Darío
Gil Lorenzo, Andrea Fernanda
Manucha, Walter Ariel Fernando
Garramuño, Patricia
author_role author
author2 Mazzei, Luciana Jorgelina
Benardon, María Eugenia
Oliveros, Liliana Beatriz
Cuello Carrión, Fernando Darío
Gil Lorenzo, Andrea Fernanda
Manucha, Walter Ariel Fernando
Garramuño, Patricia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CAVEOLIN-1
eNOS
HSP70
FIBROSIS
ROSUVASTATIN
OBSTRUCTIVE NEPHROPATHY
NITRIC OXIDE
topic CAVEOLIN-1
eNOS
HSP70
FIBROSIS
ROSUVASTATIN
OBSTRUCTIVE NEPHROPATHY
NITRIC OXIDE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Evidence suggesting that statins may contribute to renoprotection has been provided in experimental 28 and clinical studies. Statins restore endothelial nitric oxide (NO) levels by mechanisms including up-reg- 29 ulation of endothelial NO synthase (eNOS) expression. Caveolin-1/eNOS interaction is essential prevent- 30 ing inadequate NO levels. Here, we evaluated whether caveolin-1 associated with eNOS/Hsp70 31 expression may be involved in the mechanism by which rosuvastatin exerts tubulointerstitial fibrosis 32 protection in neonatal unilateral ureteral obstruction (UUO). Neonatal rats subjected to UUO within 33 2 days of birth and controls were treated daily with vehicle or rosuvastatin (10 mg/kg/day) by oral gavage 34 for 14 days. 35 After UUO, morphometric evaluation of interstitial fibrosis showed increased interstitial volume (Vv) 36 associated with reduced NO availability, increased mRNA and protein caveolin-1 expression as well as 37 downregulation eNOS and heat shock protein 70 (Hsp70) expression. Conversely, rosuvastatin treatment 38 attenuated the fibrotic response linked to high NO availability, decreased mRNA and protein caveolin-1 39 expression, and marked upregulation of eNOS and Hsp70 expression at transcriptional and posttranscrip- 40 tional levels. Moreover, protein?protein interactions determined by immunoprecipitation and by immu- 41 nofluorescence co-localization have shown decreased caveolin-1/eNOS as well as increased Hsp70/eNOS 42 interaction, after rosuvastatin treatment. A dose dependent effect of rosuvastatin on decreased caveolin-1 43 expression was shown in control cortex. 44 In conclusion, our data suggest that statins contribute to the protection against tubulointerstitial fibro- 45 sis injury in neonatal early kidney obstruction by increased NO availability, involving interaction of up- 46 regulated eNOS/Hsp70 and down-regulated caveolin-1.
Fil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Fil: Oliveros, Liliana Beatriz. Universidad Nacional de San Luis; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
Fil: Garramuño, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina
description Evidence suggesting that statins may contribute to renoprotection has been provided in experimental 28 and clinical studies. Statins restore endothelial nitric oxide (NO) levels by mechanisms including up-reg- 29 ulation of endothelial NO synthase (eNOS) expression. Caveolin-1/eNOS interaction is essential prevent- 30 ing inadequate NO levels. Here, we evaluated whether caveolin-1 associated with eNOS/Hsp70 31 expression may be involved in the mechanism by which rosuvastatin exerts tubulointerstitial fibrosis 32 protection in neonatal unilateral ureteral obstruction (UUO). Neonatal rats subjected to UUO within 33 2 days of birth and controls were treated daily with vehicle or rosuvastatin (10 mg/kg/day) by oral gavage 34 for 14 days. 35 After UUO, morphometric evaluation of interstitial fibrosis showed increased interstitial volume (Vv) 36 associated with reduced NO availability, increased mRNA and protein caveolin-1 expression as well as 37 downregulation eNOS and heat shock protein 70 (Hsp70) expression. Conversely, rosuvastatin treatment 38 attenuated the fibrotic response linked to high NO availability, decreased mRNA and protein caveolin-1 39 expression, and marked upregulation of eNOS and Hsp70 expression at transcriptional and posttranscrip- 40 tional levels. Moreover, protein?protein interactions determined by immunoprecipitation and by immu- 41 nofluorescence co-localization have shown decreased caveolin-1/eNOS as well as increased Hsp70/eNOS 42 interaction, after rosuvastatin treatment. A dose dependent effect of rosuvastatin on decreased caveolin-1 43 expression was shown in control cortex. 44 In conclusion, our data suggest that statins contribute to the protection against tubulointerstitial fibro- 45 sis injury in neonatal early kidney obstruction by increased NO availability, involving interaction of up- 46 regulated eNOS/Hsp70 and down-regulated caveolin-1.
publishDate 2012
dc.date.none.fl_str_mv 2012-08
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/11336/270604
García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Benardon, María Eugenia; Oliveros, Liliana Beatriz; Cuello Carrión, Fernando Darío; et al.; Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy; Academic Press Inc Elsevier Science; Nitric Oxide-Biology and Chemistry; 27; 2; 8-2012; 95-105
1089-8603
CONICET Digital
CONICET
url http://hdl.handle.net/11336/270604
identifier_str_mv García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Benardon, María Eugenia; Oliveros, Liliana Beatriz; Cuello Carrión, Fernando Darío; et al.; Caveolin-1–eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy; Academic Press Inc Elsevier Science; Nitric Oxide-Biology and Chemistry; 27; 2; 8-2012; 95-105
1089-8603
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.niox.2012.05.006
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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 13.22299

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