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学科主题: 临床医学
题名:
Cyclosporine A protects podocytes by regulating WAVE1 phosphorylation
作者: Li, Xuejuan1; Ding, Fangrui1; Wang, Suxia2; Li, Baihong1; Ding, Jie1
刊名: SCIENTIFIC REPORTS
发表日期: 2015-12-04
DOI: 10.1038/srep17694
卷: 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
所属项目编号: 2012CB517700 ; 30830105 ; 81170657
项目资助者: National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases
WOS记录号: WOS:000365821100002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63735
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: 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

Recommended Citation:
Li, Xuejuan,Ding, Fangrui,Wang, Suxia,et al. Cyclosporine A protects podocytes by regulating WAVE1 phosphorylation[J]. SCIENTIFIC REPORTS,2015,5.
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