LAUSR

Focal segmental glomerulosclerosis (FSGS), a podocytopathy, is one of the most common primary glomerular diseases causing end-stage renal disease in children. Its mechanisms remain unclear and the effective treatment lacks. MiR-155 is a typical multifunctional miRNA, which serves a crucial role in the regulation of numerous vessel cells. The present study aimed to investigate the role of miR-155 in the pathogenesis of FSGS. A FSGS model was establishe by injection of adriamycin in miR-155 knockout mice. Renal pathological changes were observed by Periodic Schiff-Methenamine Silver staining and Masson trichrome staining. Podocyte morphology and autophagosomes were examined with electron microscopy. Podocyte density was estimated by the Weibel-Gomez method. Expression of autophagy markers and apoptosis-associated proteins were analyzed by Western blotting analysis. Silencing of miR-155 significantly decreased urinary protein excretion and ameliorated glomerulosclerosis in adriamycin-induced FSGS mice. We found that adriamycin treatment led to fusion of podocyte foot processes, swelling of the podocyte body, dilated mitochondria, and podocyte loss. Inhibition of miR-155 improved podocyte depletion and the above cytopathies induced by adriamycin. In addition, the results also demonstrated that in miR-155 KO mice, the expression of LC3 and ATG5 was increased and the expression of P62 was decreased. These suggest that modulated miR-155 can prevent podocyte damage, by regulating the level of autophagy. The present study provides a novel insight into microRNAs as potential therapeutics for the treatment of podocytopathy.