Calpastatin prevents Angiotensin II–mediated podocyte injury through maintenance of autophagy

• DOI: 10.1016/j.kint.2021.02.024
• Publication Date: 2021-03-05T18:42:36Z
• Authors: Imane Bensaada; Blaise Robin; Joëlle Perez; Yann Salemkour; Anna Chipont; Marine Camus; Mathilde Lemoine; Lea Guyonnet; Hélène Lazareth; Emmanuel Letavernier; Carole Hénique; Pierre-Louis Tharaux; Olivia Lenoir
• Keywords: Calpastatin

The strong predictive value of proteinuria in chronic glomerulopathies is firmly established as well the pathogenic role angiotensin II promoting progression glomerular disease with an altered filtration barrier, podocyte injury and scarring glomeruli. Here we found that II-induced hypertension inhibited autophagy flux mouse Deletion Atg5 (a gene encoding a protein involved autophagy) specifically resulted accelerated podocytopathy, accentuated albuminuria glomerulosclerosis. This indicates key protective mechanism this condition. Angiotensin-II induced calpain activity podocytes inhibits flux. Podocytes from mice transgenic expression endogenous inhibitor calpastatin displayed higher at baseline was resistant to II-dependent inhibition. Also, sustained limited damage albuminuria. These findings suggest has effects on structure function, part through activation calpains leading blockade autophagy. uncover original whereby II-mediated via calcium-induced recruitment consequences case imbalance by activity. Thus, preventing calpain-mediated decrease may be promising new therapeutic strategy for nephropathies associated high renin-angiotensin system