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微小RNA-155通过靶向BACH1增强β地中海贫血/HbE单核细胞的吞噬活性。

MiR-155 enhances phagocytic activity of β-thalassemia/HbE monocytes via targeting of BACH1.

作者信息

Srinoun Kanitta, Nopparatana Chamnong, Wongchanchailert Malai, Fucharoen Suthat

机构信息

Faculty of Medical Technology, Prince of Songkla University, 15, Kanjanavanit Rd., Hat Yai, Songkhla, 90110, Thailand.

Department of Pathology, Faculty of Medicine, Prince of Songkla University, 25/25, Putthamonthon 4 Rd., Salaya, Putthamonthon, Nakron Pratom, 73170, Thailand.

出版信息

Int J Hematol. 2017 Nov;106(5):638-647. doi: 10.1007/s12185-017-2291-4. Epub 2017 Jul 6.

Abstract

Abnormal red blood cell (RBC) clearance in β-thalassemia is triggered by activated monocytes. Recent reports indicate that miRNA (miR-) plays a role in monocyte activation. To study phagocytic function, we co-cultured monocytes of normal, non-splenectomized and splenectomized β-thalassemia/HbE individuals with RBCs obtained from normal, non-splenectomized and splenectomized β-thalassemia/HbE individuals. The phagocytic activity of β-thalassemia/HbE monocytes co-cultured with β-thalassemia/HbE RBCs was significantly higher than that of normal monocytes co-cultured with normal RBCs. Upregulation of monocyte miR-155 was observed in β-thalassemia/HbE patients. Increased miR-155 was associated with reductions in BTB and CNC Homology1 (BACH1) target gene expression and increased phagocytic activity of β-thalassemia/HbE monocytes. Taken together, these findings suggested that increased miR-155 expression in activated monocytes leads to enhanced phagocytic activity via BACH-1 regulation in β-thalassemia/HbE. This provides novel insights into the phagocytic clearance of abnormal RBCs in β-thalassemia/HbE.

摘要

β地中海贫血中异常红细胞(RBC)清除是由活化的单核细胞触发的。最近的报告表明,微小RNA(miR-)在单核细胞活化中起作用。为了研究吞噬功能,我们将正常、未行脾切除术和行脾切除术的β地中海贫血/HbE个体的单核细胞与从正常、未行脾切除术和行脾切除术的β地中海贫血/HbE个体获得的红细胞进行共培养。与正常红细胞共培养的正常单核细胞相比,与β地中海贫血/HbE红细胞共培养的β地中海贫血/HbE单核细胞的吞噬活性显著更高。在β地中海贫血/HbE患者中观察到单核细胞miR-155上调。miR-155增加与BTB和CNC同源物1(BACH1)靶基因表达降低以及β地中海贫血/HbE单核细胞吞噬活性增加有关。综上所述,这些发现表明,活化单核细胞中miR-155表达增加通过β地中海贫血/HbE中的BACH-1调节导致吞噬活性增强。这为β地中海贫血/HbE中异常红细胞的吞噬清除提供了新的见解。

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