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Cyclosporine A protects podocytes by regulating WAVE1 phosphorylation
Li, Xuejuan1; Ding, Fangrui1; Wang, Suxia2; Li, Baihong1; Ding, Jie1
刊名SCIENTIFIC REPORTS
2015-12-04
DOI10.1038/srep17694
5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]FOCAL SEGMENTAL GLOMERULOSCLEROSIS ; ARP2/3 COMPLEX ; ALPORT-SYNDROME ; CELL-MIGRATION ; ACTIN ; STABILIZATION ; DISEASE ; WASP ; LAMELLIPODIA ; PROTEINURIA
英文摘要

Accumulating evidence suggests that podocytes are direct targets of many classic antiproteinuric drugs. The immunosuppressive drug cyclosporine A (CsA), which is a calcineurin inhibitor, is used to treat proteinuric kidney diseases. One novel mechanism by which CsA reduces proteinuria is by directly stabilizing the podocyte cytoskeleton. Previous studies showed that calcineurin can directly regulate WAVE1 within mouse striatal slices. In this study, WAVE1 was expressed in podocytes and was localized in the podocyte cell bodies and foot processes (FPs). WAVE1 expression increased in both in vivo and in vitro models of puromycin aminonucleoside (PAN)-induced podocyte injury. CsA restored WAVE1 expression and also partially rescued the disordered F-actin arrangement after PAN injury. Co-immunoprecipitation assays showed that calcineurin directly interacted with WAVE1 and regulated WAVE1 phosphorylation in podocytes. Synaptopodin is a well-characterized target of CsA. WAVE1 overexpression and synaptopodin knockdown experiments directly demonstrated that WAVE1 expression is not dependent on synaptopodin expression, and vice versa. Overexpression of WAVE1 using a WAVE1 plasmid disrupted F-actin structure and promoted podocyte migration compared with the empty vector group. Therefore, WAVE1 may be a novel molecular target for the maintenance of podocyte FPs and for antiproteinuric treatment in the future.

语种英语
WOS记录号WOS:000365821100002
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被引频次:3[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/400002259/63735
专题北京大学第一临床医学院_儿科
北京大学第一临床医学院_电镜室
作者单位1.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
2.Peking Univ, Hosp 1, Electron Microscopy Lab, Beijing 100034, Peoples R China
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Li, Xuejuan,Ding, Fangrui,Wang, Suxia,et al. Cyclosporine A protects podocytes by regulating WAVE1 phosphorylation[J]. SCIENTIFIC REPORTS,2015,5.
APA Li, Xuejuan,Ding, Fangrui,Wang, Suxia,Li, Baihong,&Ding, Jie.(2015).Cyclosporine A protects podocytes by regulating WAVE1 phosphorylation.SCIENTIFIC REPORTS,5.
MLA Li, Xuejuan,et al."Cyclosporine A protects podocytes by regulating WAVE1 phosphorylation".SCIENTIFIC REPORTS 5(2015).
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