Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship

Autores
Giraud Billoud, Maximiliano German; Fader Kaiser, Claudio Marcelo; Agüero, Rocio; Ezquer, Fernando; Ezquer, Eduardo Marcelo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Diabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, the pathophysiological mechanisms that determine its development and progression have not yet been elucidated. In the present study, we evaluate the role of autophagy at early stages of DN, induced in type 2 diabetes mellitus (T2DM) mouse, and its association with proximal tubule membrane endocytic receptors, megalin and cubilin. In T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but an absence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group, and an increase in the number of these vesicles marked with LBPA by immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex. These results indicate an alteration of the tubular endocytic transporters in DN, which could be related to autophagic dysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of this disease.
Fil: Giraud Billoud, Maximiliano German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Fader Kaiser, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Agüero, Rocio. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Ezquer, Fernando. Universidad del Desarrollo; Chile
Fil: Ezquer, Marcelo. Universidad del Desarrollo; Chile
Materia
MEGALIN
CUBILIN
TYPE 2 DIABETES MELLITUS
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:11336/96112
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/96112
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationshipGiraud Billoud, Maximiliano GermanFader Kaiser, Claudio MarceloAgüero, RocioEzquer, FernandoEzquer, Eduardo MarceloMEGALINCUBILINTYPE 2 DIABETES MELLITUShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Diabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, the pathophysiological mechanisms that determine its development and progression have not yet been elucidated. In the present study, we evaluate the role of autophagy at early stages of DN, induced in type 2 diabetes mellitus (T2DM) mouse, and its association with proximal tubule membrane endocytic receptors, megalin and cubilin. In T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but an absence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group, and an increase in the number of these vesicles marked with LBPA by immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex. These results indicate an alteration of the tubular endocytic transporters in DN, which could be related to autophagic dysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of this disease.Fil: Giraud Billoud, Maximiliano German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Fader Kaiser, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Agüero, Rocio. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Ezquer, Fernando. Universidad del Desarrollo; ChileFil: Ezquer, Marcelo. Universidad del Desarrollo; ChileInstituto de Histología y Embriología Dr. Mario Burgos2018-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96112Giraud Billoud, Maximiliano German; Fader Kaiser, Claudio Marcelo; Agüero, Rocio; Ezquer, Fernando; Ezquer, Eduardo Marcelo; Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship; Instituto de Histología y Embriología Dr. Mario Burgos; Biocell; 42; 2; 11-2018; 35-401667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mendoza.conicet.gov.ar/portal//biocell/vol/pdf/42_2/(1)7010%20Giraud-Billoud%20Ef.pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:38Zoai:ri.conicet.gov.ar:11336/96112instacron: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 10:01:38.527CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
title Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
spellingShingle Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
Giraud Billoud, Maximiliano German
MEGALIN
CUBILIN
TYPE 2 DIABETES MELLITUS
title_short Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
title_full Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
title_fullStr Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
title_full_unstemmed Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
title_sort Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
dc.creator.none.fl_str_mv Giraud Billoud, Maximiliano German
Fader Kaiser, Claudio Marcelo
Agüero, Rocio
Ezquer, Fernando
Ezquer, Eduardo Marcelo
author Giraud Billoud, Maximiliano German
author_facet Giraud Billoud, Maximiliano German
Fader Kaiser, Claudio Marcelo
Agüero, Rocio
Ezquer, Fernando
Ezquer, Eduardo Marcelo
author_role author
author2 Fader Kaiser, Claudio Marcelo
Agüero, Rocio
Ezquer, Fernando
Ezquer, Eduardo Marcelo
author2_role author
author
author
author
dc.subject.none.fl_str_mv MEGALIN
CUBILIN
TYPE 2 DIABETES MELLITUS
topic MEGALIN
CUBILIN
TYPE 2 DIABETES MELLITUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Diabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, the pathophysiological mechanisms that determine its development and progression have not yet been elucidated. In the present study, we evaluate the role of autophagy at early stages of DN, induced in type 2 diabetes mellitus (T2DM) mouse, and its association with proximal tubule membrane endocytic receptors, megalin and cubilin. In T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but an absence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group, and an increase in the number of these vesicles marked with LBPA by immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex. These results indicate an alteration of the tubular endocytic transporters in DN, which could be related to autophagic dysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of this disease.
Fil: Giraud Billoud, Maximiliano German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Fader Kaiser, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Agüero, Rocio. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Ezquer, Fernando. Universidad del Desarrollo; Chile
Fil: Ezquer, Marcelo. Universidad del Desarrollo; Chile
description Diabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, the pathophysiological mechanisms that determine its development and progression have not yet been elucidated. In the present study, we evaluate the role of autophagy at early stages of DN, induced in type 2 diabetes mellitus (T2DM) mouse, and its association with proximal tubule membrane endocytic receptors, megalin and cubilin. In T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but an absence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group, and an increase in the number of these vesicles marked with LBPA by immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex. These results indicate an alteration of the tubular endocytic transporters in DN, which could be related to autophagic dysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of this disease.
publishDate 2018
dc.date.none.fl_str_mv 2018-11
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/11336/96112
Giraud Billoud, Maximiliano German; Fader Kaiser, Claudio Marcelo; Agüero, Rocio; Ezquer, Fernando; Ezquer, Eduardo Marcelo; Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship; Instituto de Histología y Embriología Dr. Mario Burgos; Biocell; 42; 2; 11-2018; 35-40
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96112
identifier_str_mv Giraud Billoud, Maximiliano German; Fader Kaiser, Claudio Marcelo; Agüero, Rocio; Ezquer, Fernando; Ezquer, Eduardo Marcelo; Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship; Instituto de Histología y Embriología Dr. Mario Burgos; Biocell; 42; 2; 11-2018; 35-40
1667-5746
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.mendoza.conicet.gov.ar/portal//biocell/vol/pdf/42_2/(1)7010%20Giraud-Billoud%20Ef.pdf
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
dc.publisher.none.fl_str_mv Instituto de Histología y Embriología Dr. Mario Burgos
publisher.none.fl_str_mv Instituto de Histología y Embriología Dr. Mario Burgos
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_ 1842269708609388544
score 13.13397

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