Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus

Autores
Giraud Billoud, Maximiliano German; Ezquer, Fernando; Bahamonde, Javiera; Ezquer, Marcelo
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A decrease in the tubular expression of albumin endocytic transporters megalin and cubilin has been associated with diabetic nephropathy (DN), but there are no comprehensive studies to date relating early tubulointerstitial injury and the effect of the disease on both transporters in type 1 diabetes mellitus (T1DM). We used eight-week-old male C57BL/6 mice divided into two groups; one of them received the vehicle (control group), while the other received the vehicle + 200 mg/kg streptozotocin (T1DM). Ten weeks after the injection, we evaluated plasma insulin, enzymuria, urinary vitamin D-binding protein (VDBP), tubulointerstitial fibrosis and proximal tubule histology, markers of autophagy, and megalin and cubilin levels. We found a reduction in tubular protein reabsorption (albumin and VDBP as specific substances carried by both transporters) with increased tubulointerstitial injury, development of fibrosis, thickening of tubular basement membrane, and an increase in tubular cell metalloproteases. This was associated with a decrease in the renal expression of megalin and cubilin. We also observed an increase in the amount of cellular vesicles of the phagocytic system in the tubules, which could be linked to an alteration of normal intracellular trafficking of both receptors, thus affecting the normal function of transporters in early stages of DN. In diabetic animals, the added effects of tubulointerstitial injury, the decreases in megalin and cubilin expression, and an altered intracellular trafficking of these receptors, seriously affect protein reabsorption
Fil: Giraud Billoud, Maximiliano German. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile. 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 Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Ezquer, Fernando. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile
Fil: Bahamonde, Javiera. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile
Fil: Ezquer, Marcelo. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile
Materia
Albuminuria
Megalin
Cubilin
Autophagy
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:11336/49428
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/49428
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitusGiraud Billoud, Maximiliano GermanEzquer, FernandoBahamonde, JavieraEzquer, MarceloAlbuminuriaMegalinCubilinAutophagyhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3A decrease in the tubular expression of albumin endocytic transporters megalin and cubilin has been associated with diabetic nephropathy (DN), but there are no comprehensive studies to date relating early tubulointerstitial injury and the effect of the disease on both transporters in type 1 diabetes mellitus (T1DM). We used eight-week-old male C57BL/6 mice divided into two groups; one of them received the vehicle (control group), while the other received the vehicle + 200 mg/kg streptozotocin (T1DM). Ten weeks after the injection, we evaluated plasma insulin, enzymuria, urinary vitamin D-binding protein (VDBP), tubulointerstitial fibrosis and proximal tubule histology, markers of autophagy, and megalin and cubilin levels. We found a reduction in tubular protein reabsorption (albumin and VDBP as specific substances carried by both transporters) with increased tubulointerstitial injury, development of fibrosis, thickening of tubular basement membrane, and an increase in tubular cell metalloproteases. This was associated with a decrease in the renal expression of megalin and cubilin. We also observed an increase in the amount of cellular vesicles of the phagocytic system in the tubules, which could be linked to an alteration of normal intracellular trafficking of both receptors, thus affecting the normal function of transporters in early stages of DN. In diabetic animals, the added effects of tubulointerstitial injury, the decreases in megalin and cubilin expression, and an altered intracellular trafficking of these receptors, seriously affect protein reabsorptionFil: Giraud Billoud, Maximiliano German. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile. 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 Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ezquer, Fernando. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Bahamonde, Javiera. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Ezquer, Marcelo. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileInstituto de Histología y Embriología “Dr. Mario H. Burgos”2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49428Giraud Billoud, Maximiliano German; Ezquer, Fernando; Bahamonde, Javiera; Ezquer, Marcelo; Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus; Instituto de Histología y Embriología “Dr. Mario H. Burgos”; Biocell; 41; 1; 1-2017; 1-121667-57460327-9545CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.cricyt.edu.ar/biocell/vol/41_I_1.htmlinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:54Zoai:ri.conicet.gov.ar:11336/49428instacron: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 10:02:55.742CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
title Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
spellingShingle Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
Giraud Billoud, Maximiliano German
Albuminuria
Megalin
Cubilin
Autophagy
title_short Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
title_full Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
title_fullStr Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
title_full_unstemmed Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
title_sort Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus
dc.creator.none.fl_str_mv Giraud Billoud, Maximiliano German
Ezquer, Fernando
Bahamonde, Javiera
Ezquer, Marcelo
author Giraud Billoud, Maximiliano German
author_facet Giraud Billoud, Maximiliano German
Ezquer, Fernando
Bahamonde, Javiera
Ezquer, Marcelo
author_role author
author2 Ezquer, Fernando
Bahamonde, Javiera
Ezquer, Marcelo
author2_role author
author
author
dc.subject.none.fl_str_mv Albuminuria
Megalin
Cubilin
Autophagy
topic Albuminuria
Megalin
Cubilin
Autophagy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv A decrease in the tubular expression of albumin endocytic transporters megalin and cubilin has been associated with diabetic nephropathy (DN), but there are no comprehensive studies to date relating early tubulointerstitial injury and the effect of the disease on both transporters in type 1 diabetes mellitus (T1DM). We used eight-week-old male C57BL/6 mice divided into two groups; one of them received the vehicle (control group), while the other received the vehicle + 200 mg/kg streptozotocin (T1DM). Ten weeks after the injection, we evaluated plasma insulin, enzymuria, urinary vitamin D-binding protein (VDBP), tubulointerstitial fibrosis and proximal tubule histology, markers of autophagy, and megalin and cubilin levels. We found a reduction in tubular protein reabsorption (albumin and VDBP as specific substances carried by both transporters) with increased tubulointerstitial injury, development of fibrosis, thickening of tubular basement membrane, and an increase in tubular cell metalloproteases. This was associated with a decrease in the renal expression of megalin and cubilin. We also observed an increase in the amount of cellular vesicles of the phagocytic system in the tubules, which could be linked to an alteration of normal intracellular trafficking of both receptors, thus affecting the normal function of transporters in early stages of DN. In diabetic animals, the added effects of tubulointerstitial injury, the decreases in megalin and cubilin expression, and an altered intracellular trafficking of these receptors, seriously affect protein reabsorption
Fil: Giraud Billoud, Maximiliano German. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile. 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 Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Ezquer, Fernando. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile
Fil: Bahamonde, Javiera. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile
Fil: Ezquer, Marcelo. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile
description A decrease in the tubular expression of albumin endocytic transporters megalin and cubilin has been associated with diabetic nephropathy (DN), but there are no comprehensive studies to date relating early tubulointerstitial injury and the effect of the disease on both transporters in type 1 diabetes mellitus (T1DM). We used eight-week-old male C57BL/6 mice divided into two groups; one of them received the vehicle (control group), while the other received the vehicle + 200 mg/kg streptozotocin (T1DM). Ten weeks after the injection, we evaluated plasma insulin, enzymuria, urinary vitamin D-binding protein (VDBP), tubulointerstitial fibrosis and proximal tubule histology, markers of autophagy, and megalin and cubilin levels. We found a reduction in tubular protein reabsorption (albumin and VDBP as specific substances carried by both transporters) with increased tubulointerstitial injury, development of fibrosis, thickening of tubular basement membrane, and an increase in tubular cell metalloproteases. This was associated with a decrease in the renal expression of megalin and cubilin. We also observed an increase in the amount of cellular vesicles of the phagocytic system in the tubules, which could be linked to an alteration of normal intracellular trafficking of both receptors, thus affecting the normal function of transporters in early stages of DN. In diabetic animals, the added effects of tubulointerstitial injury, the decreases in megalin and cubilin expression, and an altered intracellular trafficking of these receptors, seriously affect protein reabsorption
publishDate 2017
dc.date.none.fl_str_mv 2017-01
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/11336/49428
Giraud Billoud, Maximiliano German; Ezquer, Fernando; Bahamonde, Javiera; Ezquer, Marcelo; Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus; Instituto de Histología y Embriología “Dr. Mario H. Burgos”; Biocell; 41; 1; 1-2017; 1-12
1667-5746
0327-9545
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49428
identifier_str_mv Giraud Billoud, Maximiliano German; Ezquer, Fernando; Bahamonde, Javiera; Ezquer, Marcelo; Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus; Instituto de Histología y Embriología “Dr. Mario H. Burgos”; Biocell; 41; 1; 1-2017; 1-12
1667-5746
0327-9545
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.cricyt.edu.ar/biocell/vol/41_I_1.html
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 Instituto de Histología y Embriología “Dr. Mario H. Burgos”
publisher.none.fl_str_mv Instituto de Histología y Embriología “Dr. Mario H. 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_ 1842269776032825344
score 13.13397

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