Vincristine alleviates adriamycin-induced nephropathy through stabilizing actin cytoskeleton

作者：Lei Yin, Youying Mao, Hejie Song, Ye Wang, Wei Zhou, Zhen Zhang · 发表于：Cell & Bioscience · 年份：2017 · DOI：10.1186/s13578-016-0129-z · 被引用次数：34 · 研究领域：Renal Diseases and Glomerulopathies、Chronic Kidney Disease and Diabetes、Coagulation, Bradykinin, Polyphosphates, and Angioedema

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.