LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway

LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway
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DOI:
10.1186/s13578-019-0346-3
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发表时间:
2019-10-15
影响因子:
7.5
通讯作者:
Han, Liping
Han, Liping
中科院分区:
生物学2区
文献类型:
--
作者:
Liu, Zheying;Liu, Liya;Han, Liping

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目的探讨LncRNA H19在子宫内膜异位症(EMS)患者Th 17细胞分化和子宫内膜基质细胞(ESCs)增殖中的作用机制。方法采用qRT-PCR和western blot检测LncRNA H19、miR-342- 3 p和IER 3的表达。流式细胞仪检测Th 17细胞/CD 4 + T细胞的比例。ELISA法检测IL-17水平。通过荧光素酶报告基因分析证实miR-342- 3 p与IER 3的相互作用。结果EMS组和Th 17分化组患者腹腔液单个核细胞(PFMCs)中LncRNA H19和IER 3表达下调,而miR-342- 3 p表达上调,Th 17细胞比例增加。过表达LncRNA H19可降低IL-17水平和Th 17/CD 4 + T细胞比例。此外,我们证实miR-342- 3 p可以靶向IER 3并负调控IER 3的表达。LncRNA H19过表达通过调节miR-342- 3 p/IER 3抑制Th 17分化和ESC增殖。体内实验显示LncRNA H19过表达抑制Th 17细胞分化诱导的类银屑病样病变的生长。结论EMS患者PFMC中LncRNA H19表达下调,LncRNA H19过表达通过miR-342- 3 p/IER 3途径抑制Th 17细胞分化和ESCs增殖。
Objective To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS). Methods LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay. Results LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions. Conclusion LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway.