单位：[1]Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China临床科室儿科儿科首都医科大学附属北京友谊医院[2]Pediatric Department, Peking University First Hospital, Beijing 100034, China
Smad3 signaling and transgelin expression are often activated during puromycin aminonucleoside (PAN)-induced podocyte injury. Here, we investigated whether the Smad3 inhibitor SIS3 can ameliorate damage to injured podocytes. A model of PAN-induced podocyte injury was constructed using the MPC5 cell line. The effects of SIS3 on the expression of the podocyte cytoskeletal proteins transgelin, p15(INK4B), phosphor-smad3, phosphor-JAK/stat3, the apoptotic marker cleaved caspase 3, and c-myc were investigated using western blot. The distribution of F-actin in PAN-induced podocyte injury was observed under an immunofluorescence microscope. PAN-induced podocyte injury altered the distribution of F-actin and transgelin, and colocalization of these two proteins was observed. Transgelin expression and Smad3 phosphorylation were increased in the MPC5 cell line with prolonged PAN treatment. In addition, c-myc expression, p15(INK4B), and JAK phosphorylation were all increased after treatment with PAN. Treatment with the Smad3 inhibitor SIS3 reversed these phenomena and protected against PAN-induced podocyte injury. Moreover, stimulating podocytes directly with TGF beta-1 also led to enhanced expression of transgelin or phosphor-JAK/stat3, and this could be inhibited by SIS3. In conclusion, transgelin expression was induced through the Smad3 signaling pathway during PAN-induced podocyte injury, and the resulting abnormal distribution of F-actin and the enhanced expression of transgelin could be reversed by blockade of this pathway.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81400718]; Research Foundation of Beijing Friendship Hospital, Capital Medical University [yyqdkt2018-21]
第一作者单位：[1]Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China
通讯作者：
通讯机构：[1]Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China[*1]Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, 95 YongAn Road, Xicheng District, Beijing 100050, China
推荐引用方式(GB/T 7714)：
Lina Jiang,Hong Cui,Jie Ding,et al.Puromycin aminonucleoside-induced podocyte injury is ameliorated by the Smad3 inhibitor SIS3[J].FEBS OPEN BIO.2020,10(8):1601-1611.doi:10.1002/2211-5463.12916.
APA：
Lina Jiang,Hong Cui,Jie Ding,Aijun Yang&Yingchao Zhang.(2020).Puromycin aminonucleoside-induced podocyte injury is ameliorated by the Smad3 inhibitor SIS3.FEBS OPEN BIO,10,(8)
MLA：
Lina Jiang,et al."Puromycin aminonucleoside-induced podocyte injury is ameliorated by the Smad3 inhibitor SIS3".FEBS OPEN BIO 10..8(2020):1601-1611
