title: Vincristine alleviates adriamycin-induced nephropathy through stabilizing actin cytoskeleton.
abstract: 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.
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Youying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China ; Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hejie
authors.initials: H
authors.lastname: Song
authors.affiliation: Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China ; Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China ; Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhen
authors.identifier: 0000-0002-9898-054X
authors.initials: Z
authors.lastname: Zhang
keywords: Actin cytoskeleton; Focal adhesion kinase; Integrin; Nephrotic syndrome; Vincristine