Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship
| Autor: | Fernando Ezquer, Rocio Agüero, Claudio Marcelo Fader Kaiser, Maximiliano German Giraud Billoud, Eduardo Marcelo Ezquer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MEGALIN medicine.medical_specialty business.industry Endocytic cycle Autophagy General Medicine Bioquímica y Biología Molecular CUBILIN Cubilin medicine.disease Ciencias Biológicas purl.org/becyt/ford/1 [https] Diabetic nephropathy 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Endocrinology Internal medicine medicine TYPE 2 DIABETES MELLITUS Proximal tubule purl.org/becyt/ford/1.6 [https] business CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Scopus-Elsevier |
| ISSN: | 1667-5746 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|