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

GIRAUD BILLOUD, M.; FADER-KAISER, C; AGÜERO, R; EZQUER, FE; EZQUER, ME

BIOCELL

Tech Science Press

Lugar: Nevada; Año: 2018 vol. 42 p. 35 - 40

0327-9545

Diabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, thepathophysiological mechanisms that determine its development and progression have not yet been elucidated. In thepresent 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 T2DManimals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but anabsence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicleslarger than those observed in the control group, and an increase in the number of these vesicles marked with LBPAby immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 proteinexpression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin Dbinding-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 autophagicdysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of thisdisease.