MicroRNA let-7i通过Janus激酶1信号转导因子及转录活化因子3信号通路调节树突状细胞针对干扰素-10的成熟,继而导致小鼠心脏移植存活时间延长

MicroRNA let-7i regulates dendritic cells maturation targeting interleukin-10 via the Janus kinase 1-signal transducer and activator of transcription 3 signal pathway subsequently induces prolonged cardiac allograft survival in rats
2016-08-19 11:27发表评论
作者:Sun, Y., Jin, X., Liu, X., Zhang, M., Liu, W., Li, Z., Han, N., Tan, M., Chi, D., Zhu, J., Zhang, B., Yu, B., Wu, J.
机构: 心肌缺血教育部重点实验室
期刊: J HEART LUNG TRANSPL2016年3月3期35卷

Background In this study, we investig1ated whether microRNA let-7i regulates dendric cell maturation targeting interleukin-10 (IL-10) via the Janus kinase 1-signal transducer and activator of transcription 3 (JAK1-STAT3) signal pathway subsequently prolongs rat cardiac allograft survival. Methods Quantitative real-time reverse transcriptase polymerase chain reaction, enzyme linked immunosorbent assay, and dual-luciferase assay were performed to verify whether IL-10 was the target of let-7i, and regulatory T cells were assessed by flow cytometry and immunohistochemical study. Western blot was performed to detect JAK1, STAT3, and phosphorylated STAT3 expression. Lewis recipients of Dark Agouti hearts were transfused with phosphate-buffered saline, lipopolysaccharide (LPS)-mature dendritic cells (mDCs), or let-7i-inhibitor-mDCs. Allograft survival times were recorded, and histologic studies were performed. Results Expression of IL-10 messenger RNA level and production of IL-10 were increased in let-7i-inhibitor-mDCs compared with LPS-mDCs. Luciferase activity showed that the translational level of the IL-10 luciferase reporter was decreased by let-7i mimic but increased by let-7i-inhibitor. MicroRNA let-7i inhibitor suppressed DC maturation; however, pretreatment of IL-10 small interfering RNA attenuated the suppression. Expression of JAK1, STAT3, and phosphorylated STAT3 in mDCs were suppressed by let-7i mimic, and pre-treatment of IL-10 small interfering RNA, however, were upregulated by let-7i inhibitor. Lewis recipients transfused with let-7i-inhibitor-mDCs significantly prolonged Dark Agouti cardiac allograft survival. The allografts transfused with let-7i-inhibitor-mDCs showed slight cell infiltration and significantly preserved graft structure. Inhibition of let-7i increased CD4+CD25+forkhead box P3+ regulatory T cells and modulated cytokine profiles in vivo and in vitro. Conclusions MicroRNA let-7i regulated DC maturation and function targeting IL-10 through the JAK1-STAT3 pathway. Moreover, transfusion of LPS-induced mDCs transfected with let-7i inhibitor induced prolonged cardiac allograft survival and generated regulatory T cells.

© 2016 International Society for Heart and Lung Transplantation.

通讯机构: Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
学科代码:心血管病学 呼吸病学   关键词:MicroRNA let-7i通过Janus激酶1信号转导因 树突状细胞 干扰素-10 小鼠心脏移植存 ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
Scopus介绍:Scopus 于2004年11月正式推出,是目前全球规模最大的文摘和引文数据库。Scopus涵盖了由5000多家出版商出版发行的科技、医学和社会科学方面的18,000多种期刊,其中同行评审期刊16,500多种。相对于其他单一的文摘索引数据库而言,Scopus的内容更加全面,学科更加广泛,特别是在获取欧洲及亚太地区的文献方面,用户可检索出更多的文献数量。通过Scopus,用户可以检索到1823年以来的近4000万条摘要和题录信息,以及1996年以来所引用的参考文献。数据每日更新。 马上访问Scopus网站http://www.scopus.com/
顶一下(0
您可能感兴趣的文章
    发表评论网友评论(0)
      发表评论
      登录后方可发表评论,点击此处登录