Calcineurin Inhibitors Cyclosporin A and Tacrolimus Protect Against Podocyte Injury Induced by Puromycin Aminonucleoside in Rodent Models

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 2

PMID 27580845

Citations 37

Authors

Xiujin Shen

Hong Jiang

Meike Ying

Zhoutao Xie

Xiayu Li

Haibing Wang

Jie Zhao

Chuan Lin

Yucheng Wang

Shi Feng

Jia Shen

Chunhua Weng

Weiqiang Lin

Huiping Wang

Qin Zhou

Yan Bi

Meng Li

Lingyan Wang

Tongyu Zhu

Xiaoru Huang

Hui-Yao Lan

Jing Zhou

Jianghua Chen

Affiliations

Soon will be listed here.

Abstract

Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway.

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