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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/270604
Ver los metadatos del registro completo
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 Técnicas2025-09-29T09:33:07Zoai: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:34982025-09-29 09:33:07.377CONICET 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 |
_version_ |
1844613014966239232 |
score |
13.070432 |