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学科主题临床医学
Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in the unphosphorylated state
Li, Xiaoyan; Zhang, Xiaoyan; Li, Xuejuan; Wang, Xuejing; Wang, Suxia; Ding, Jie
关键词Proteinuria Cyclosporine a Cofilin-1
刊名EXPERIMENTAL BIOLOGY AND MEDICINE
2014-08-01
DOI10.1177/1535370214530365
239期:8页:922-936
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]ACTIN-DEPOLYMERIZING FACTOR ; NEPHROTIC SYNDROME ; SLIT-DIAPHRAGM ; REGULATES ACTIN ; NUCLEAR ACTIN ; LIM-KINASE ; IN-VIVO ; DYNAMICS ; NEPHRIN ; CYTOSKELETON
英文摘要

Podocyte foot process (FP) is dysregulated in nephrotic syndrome. The effacement of podocyte FPs typically arises following perturbations in the actin cytoskeleton. Recent data suggest that the effects of calcineurin (CaN) inhibitor cyclosporine A (CsA) are independent of its effects on T-cells, and CsA has been identified as stabilizing the actin cytoskeleton through stabilizing synaptopodin in podocytes, and thereby directly reducing proteinuria. Other studies showed that CsA could regulate cofilin-1 directly within tubular epithelial cells. However, whether synaptopodin is the only target of CsA or whether the antiproteinuric role of CsA is played by regulating cofilin-1 in podocytes has not been studied. In the present study, changes in the expression and distribution of nephrin, synaptopodin, cofilin-1 and phosphorylated cofilin-1 (pho-cofilin-1) were detected in both puromycin aminonucleoside (PAN) induced nephrotic rats treated with CsA and cultured podocytes exposed to PAN with/without CsA. Cofilin-1, synaptopodin mRNA was knocked down or combined by siRNA to investigate whether cofilin-1 was critical for the protective effect of CsA and whether the effect of CsA on cofilin-1 was independent of its effect on synaptopodin. We found that CsA reduced proteinuria and repaired FP effacement of PAN-induced nephropathy, restored expression of nephrin, synaptopodin, cofilin-1, pho-cofilin-1 both in vivo and in vitro. CsA also repaired actin cytoskeleton impaired by PAN in vitro. The protective effect of CsA was diminished when cofilin-1 was knocked down compared to negative control. Synaptopodin knocked down had no effect on cofilin-1. The protective effect of CsA decreased significantly when cofilin-1 and synaptopodin were simultaneously knocked down compared to only cofilin-1 knock down. In conclusion, the antiproteinuric effect of CsA is derived from the stabilization of the podocyte actin cytoskeleton by upregulating expression of cofilin-1, which was independent of its effect on synaptopodin.

语种英语
WOS记录号WOS:000342772600004
项目编号2012CB517701 ; 81170657/30830105/81200511
资助机构National Basic Research Program of China (973 Program) ; National Nature Science Foundation of China
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56883
专题北京大学第一临床医学院_电镜室
北京大学第一临床医学院_儿科
作者单位Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Li, Xiaoyan,Zhang, Xiaoyan,Li, Xuejuan,et al. Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in the unphosphorylated state[J]. EXPERIMENTAL BIOLOGY AND MEDICINE,2014,239(8):922-936.
APA Li, Xiaoyan,Zhang, Xiaoyan,Li, Xuejuan,Wang, Xuejing,Wang, Suxia,&Ding, Jie.(2014).Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in the unphosphorylated state.EXPERIMENTAL BIOLOGY AND MEDICINE,239(8),922-936.
MLA Li, Xiaoyan,et al."Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in the unphosphorylated state".EXPERIMENTAL BIOLOGY AND MEDICINE 239.8(2014):922-936.
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