title: miR-375 ameliorates sepsis by downregulating miR-21 level via inhibiting JAK2-STAT3 signaling.
abstract: 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.
authors.affiliation: Department of Intensive Care Unit, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sheng
authors.affiliation: Department of Intensive Care Unit, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Intensive Care Unit, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zang
authors.affiliation: Department of Intensive Care Unit, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhen
authors.affiliation: Department of Intensive Care Unit, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China. Electronic address: chenwei_weiwu@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C524940:MIRN21 microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: MDSCs; STAT3; Sepsis; miR-21; miR-375