Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models.
Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models.
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钙调神经磷酸酶抑制剂环孢菌素 A 和他克莫司可防止啮齿动物模型中嘌呤霉素氨基核苷诱导的足细胞损伤
DOI：
10.1038/srep32087
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发表时间：
2016-09-01
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Shen X;Jiang H;Ying M;Xie Z;Li X;Wang H;Zhao J;Lin C;Wang Y;Feng S;Shen J;Weng C;Lin W;Wang H;Zhou Q;Bi Y;Li M;Wang L;Zhu T;Huang X;Lan HY;Zhou J;Chen J
足细胞损伤和蛋白尿的出现是微小病变病(MCD)的特征。环孢菌素A(CsA)和他克莫司(FK506)已被报道能减少肾病综合征患者的蛋白尿，但机制尚不清楚。因此，我们研究了CsA和FK506对由氨基核苷(PAN)诱导的MCD大鼠模型和体外培养的小鼠足细胞蛋白尿的保护作用机制。我们的结果表明，CsA和FK506治疗通过减少足突融合和结蛋白，以及恢复突触素和足部蛋白来减少蛋白尿。在PAN处理的小鼠足细胞中，CsA和FK506预先孵育恢复了肌动蛋白细胞骨架的分布，增加了突触素和podocin的表达，提高了足细胞的存活率，降低了足细胞的迁移活性。CsA和FK506也可抑制PAN诱导的足细胞凋亡，这与诱导Bclxl和抑制Bax、切割caspase3和切割PARP表达有关。进一步的研究表明，CsA和FK506抑制PAN诱导的p38和JNK信号转导，从而保护足细胞免受PAN诱导的损伤。总之，CsA和FK506通过保护PAN诱导的足细胞损伤来抑制蛋白尿，这可能与抑制MAPK信号通路有关。
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) andin vitrocultured 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 beassociated with inhibition of theMAPK signaling pathway.
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影响因子：
19.6
作者：
Logar, C. M.;Brinkkoetter, P. T.;Shankland, S. J.
通讯作者：
Shankland, S. J.
影响因子：
19.6
作者：
Chen, Zhao-Hong;Qin, Wei-Song;Liu, Zhi-Hong
通讯作者：
Liu, Zhi-Hong
影响因子：
7.7
作者：
Matsuda, S;Shibasaki, F;Koyasu, S
通讯作者：
Koyasu, S
影响因子：
4.2
作者：
Dai, De-shu;Liu, Xiang;Ren, Hong-qi
通讯作者：
Ren, Hong-qi
他克莫司部分通过稳定细胞骨架和抑制足细胞凋亡来保护狼疮性肾炎足细胞免受损伤
影响因子：
3.7
作者：
Liao R;Liu Q;Zheng Z;Fan J;Peng W;Kong Q;He H;Yang S;Chen W;Tang X;Yu X
通讯作者：
Yu X