Calcineurin inhibitors ameliorate PAN‐induced podocyte injury through the NFAT–Angptl4 pathway

• DOI: 10.1002/path.5512
• Publication Date: 2020-07-20T06:04:00Z
• Authors: Xiujin Shen; Ying Zhang; Chuan Lin; Chunhua Weng; Yucheng Wang; Shi Feng; Cuili Wang; Xue Shao; Weiqiang Lin; Bingjue Li; Haibing Wang; Jianghua Chen; Hong Jiang
• Keywords: Synaptopodin; Podocin; ANGPTL4; Nephrin; NFAT

Abstract Podocyte injury plays a vital role in proteinuria and nephrotic syndrome. Calcineurin (CaN) inhibitors are effective reducing proteinuria. However, their molecular mechanism is still not fully understood. Angiopoietin‐like‐4 (ANGPTL4) secreted protein that mediates podocyte‐related nephropathy. In this study, we established puromycin aminonucleoside (PAN)‐induced minimal‐change disease (MCD) rat model cultured podocyte model. We found CaN protected against PAN‐induced injury, accompanied by an inhibition of Nfatc1 Angptl4 both vivo vitro . overexpression knockdown experiments indicated was regulated podocytes. ChIP assays further demonstrated increased expression binding to the promoter. addition, revealed directly induced rearrangement cytoskeleton podocytes, reduced synaptopodin, enhanced apoptosis. Furthermore, cohort 83 MCD 94 membranous nephropathy (MN) patients, serum ANGPTL4 compared 120 healthy controls, there were close correlations between Alb, urinary protein, eGFR, Scr, BUN patients. No obvious correlation MN Immunofluorescence studies patients located mostly conclusion, our results demonstrate ameliorate targeting through NFAT pathway, involved human © 2020 The Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.