Increased lysosomal proteolysis counteracts protein accumulation in the proximal tubule during focal segmental glomerulosclerosis

摘要: Focal segmental glomerulosclerosis (FSGS) is a prevalent cause of end-stage renal disease, but the mechanisms underlying progression are unresolved. Lysosomal protein accumulation in proximal tubule, mediated by megalin and cubilin endocytosis increased amounts filtered protein, thought to result inflammation fibrosis. Here we determine whether release inflammatory fibrotic mediators response overload tubule caused lysosomal enzyme deficits insufficient proteolysis. As model FSGS, used inducible podocyte-specific podocin-knockout mice analyzed at different time points. The content ligands lysosomes after onset proteinuria; however, mRNA levels showed only minor changes. To if elevated ligand was deficiency enzymes, enzymes found endogenous synthesis. Injection dye-quenched fluorescent iodinated albumin that proteolytic turnover knockout adapted load. Inflammatory signals were early although majority degraded endocytosed proteins effectively. Thus, degradation FSGS not fibrosis during kidney disease.