miR-375 ameliorates sepsis by downregulating miR-21 level via inhibiting JAK2-STAT3 signaling

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• 作者：Bo Sheng ; Lei Zhao ; Xuefeng Zang ; Jie Zhen ; Wei Chen ; ^{chenwei_weiwu@163.com}
• 关键词：miR-375 ; Sepsis ; MDSCs ; STAT3 ; miR-21
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：86
• 期：Complete
• 页码：254-261
• 全文大小：1690 K
• 卷排序：86

文摘

Accumulating evidences have confirmed that miRNAs have important roles in sepsis. Myeloid-derived suppressor cells (MDSCs) enhance late sepsis development through immunosuppression in mice. Here, the functions and mechanisms of miR-375 in sepsis were revealed. We found that miR-375 level was downregulated but miR-21 level was upregulated in sepsis patients and that their levels were correlated negatively. Importantly, ectopic expression of miR-375 could decrease the number of sepsis Gr1+CD11b+ MDSCs in mice. Mechanistically, miR-375 could target Janus kinase 2 (JAK2) and further impaired signal transducer and activator of transcription 3 (STAT3) in sepsis Gr1+CD11b+ MDSC. Gain and loss of function of experiments showed that upregulation or downregulation of miR-375 level could decrease or increase miR-21 level. Moreover, pretreatment of JAK2 overexpressing vector could abolish the effects of miR-375 on miR-21 level and the amount of sepsis Gr1+CD11b+ MDSCs. Therefore, our results demonstrate that miR-375 could block JAK2-STAT3 pathway and thus modulate miR-21 level, which is involved in regulation of late sepsis.