Hepatology:microRNA-155调节肝脏损伤

2018-02-11 MedSci MedSci原创

研究结论:在肝损伤过程中,miR-155在肝脏组织和循环炎性细胞的表达均发生改变,从而调节炎症细胞的招募和肝损伤。这些结果表明,维持miR-155在炎性细胞中的表达可能是调节肝损伤的一种潜在策略。

研究背景:MicroRNA-155参与免疫和炎症疾病,与肝纤维化和脂肪性肝炎相关。然而,仍不清楚miR-155参与调节肝损伤的机制。

研究方法:在野生型(WT)小鼠,miR-155(-/-)基因敲除小鼠,将野生型小鼠骨髓转移给miR-155(-/-)基因敲除的小鼠中评估miR-155在急性肝损伤中的作用。

研究结果:刀豆蛋白A(ConA)而非对乙酰氨基酚(APAP)治疗增加了野生型小鼠肝组织中miR-155的表达。相比野生型小鼠,刀豆蛋白A导致miR-155(-/-)小鼠细胞死亡和肝脏转氨酶水平和促炎细胞因子(Cxcl1, 5, 9, 10, 11, Ccl2, 20 and Icam1)水平增加。重要的是,这些动物的CD4(+) CXCR3(+)和Foxp3(+)细胞的招募显著减少,但其他炎性细胞数量没有变化。MiR-155缺乏的Treg细胞增加了Ship1的表达,Ship1是miR-155的靶标。在miR-155(-/-)基因敲除小鼠,Ship1的抑制,恢复了Foxp3(+)细胞的减少,减少了细胞因子的表达。将正常小鼠的骨髓转移给miR-155基因敲除的小鼠,部分逆转了刀豆蛋白A对miR-155(-/-)小鼠的作用(从促炎因子和细胞死亡蛋白表达上进行评估)。患有自身免疫性肝炎的患者肝组织miR-155显著增加,外周血单核细胞miR-155的表达减少。

研究结论:在肝损伤过程中,miR-155在肝脏组织和循环炎性细胞的表达均发生改变,从而调节炎症细胞的招募和肝损伤。这些结果表明,维持miR-155在炎性细胞中的表达可能是调节肝损伤的一种潜在策略。

原始出处

Blaya D, Aguilar-Bravo B, Hao F, et al. Expression of microRNA-155 in inflammatory cells modulates liver injury. Hepatology, 2018, Feb 8. doi: 10.1002/hep.29833.

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    2018-08-31 xjy02
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    2018-02-13 gwc384
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    2018-02-13 zhouqu_8