Vincristine alleviates adriamycin-induced nephropathy through stabilizing actin cytoskeleton
详细信息 查看全文
- 作者：Lei Yin ; Youying Mao ; Hejie Song ; Ye Wang ; Wei Zhou ; Zhen Zhang
- 关键词：Nephrotic syndrome ; Vincristine ; Actin cytoskeleton ; Focal adhesion kinase ; Integrin
- 刊名：Cell & Bioscience
- 出版年：2017
- 出版时间：December 2017
- 年：2017
- 卷：7
- 期：1
- 全文大小：6080KB
- 刊物主题：Cell Biology; Microbiology; Stem Cells; Neurobiology; Proteomics;
- 出版者：BioMed Central
- ISSN：2045-3701
- 卷排序：7
文摘
Antimicrotubule agent vincristine (VCR) has long been known as an alternative treatment for frequent relapse nephrotic syndrome and steroid-dependent nephrotic syndrome (SDNS). However, the mechanism is unknown. Here we found that VCR at a dosage much lower than that as an antimicrotubule agent can alleviate adriamycin (ADR)-induced proteinuria and podocyte foot process effacement. In cultured podocytes, VCR prevents ADR-induced actin fiber disorganization. In both in vitro and in vivo models, VCR suppresses ADR-induced overexpression of α3β1 integrin and focal adhesion kinase (FAK). These data suggest that VCR may relieve ADR-induced nephropathy through inhibiting injury-induced activation of integrin outside-in signaling to prevent actin cytoskeleton remodeling. Hence, our work reveals a novel role of VCR in regulating actin fiber assembly and provides first evidence on the therapeutic mechanism of VCR on nephrotic syndrome.