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学科主题: 临床医学
题名:
Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in the unphosphorylated state
作者: 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
发表日期: 2014-08-01
DOI: 10.1177/1535370214530365
卷: 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
所属项目编号: 2012CB517701 ; 81170657/30830105/81200511
项目资助者: National Basic Research Program of China (973 Program) ; National Nature Science Foundation of China
WOS记录号: WOS:000342772600004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56883
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China

Recommended Citation:
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.
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