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

Maximiliano GIRAUD-BILLOUD1,2,*, Claudio M. FADER1,3, Rocío AGÜERO2, Fernando EZQUER4, Marcelo EZQUER4

1 IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina
2 Universidad Nacional de Cuyo, Facultad de Ciencias Médicas, Instituto de Fisiología, Casilla de Correo 33, 5500-Mendoza, Argentina
3 Universidad Nacional de Cuyo, Facultad de Odontología, Casilla de Correo 33, 5500-Mendoza, Argentina
4 Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile

* Address correspondence to: M. Giraud-Billoud, email

BIOCELL 2018, 42(2), 35-40. https://doi.org/10.32604/biocell.2018.07010

Abstract

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.

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GIRAUD-BILLOUD, M., FADER, C. M., AGÜERO, R., EZQUER, F., EZQUER, M. (2018). Diabetic nephropathy, autophagy and proximal tubule protein endocytic transport: A potentially harmful relationship. BIOCELL, 42(2), 35–40.

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