MiR-22 Suppresses BMP7 in the Development of Cirrhosis
MiR-22 Suppresses BMP7 in the Development of Cirrhosis
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DOI：
10.1159/000430276
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Chen, Guofeng
中科院分区：
文献类型：
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作者：
Ji, Dong;Li, Bing;Chen, Guofeng
背景/目的：为了提高肝硬化的治疗效果，迫切需要新的预防和治疗策略。microRNAs （miRNAs）在肝硬化发病机制中的作用最近得到了承认，然而确切参与的miRNAs以及相关的分子信号通路尚未确定。具体而言，关于miR-22与骨形态发生蛋白7 （bone morphogenic protein 7, BMP7）在肝硬化发生中的关系的研究尚缺乏。方法：我们检测了肝硬化患者肝活检中miR-22与骨形态发生蛋白7 （BMP7）水平的相关性。我们检测了肝细胞中BMP7上miR-22的过表达或抑制。我们检测了miR-22与BMP7 mRNA的3'-UTR的结合。最后，在四氯化碳（CCl4）诱导的小鼠肝硬化模型中，我们给小鼠携带反义miR-22的腺相关病毒，并检测其对BMP7水平和肝硬化特征的影响。结果：患者肝组织活检中miR-22和BMP7水平呈显著负相关。MiR-22通过直接结合BMP7 mRNA的3'-UTR抑制肝细胞中BMP7的表达。反义miR-22的表达可能通过上调BMP7，显著减弱CCl4引起的肝纤维化、门脉高压和钠潴留水平。结论：MiR-22通过抑制BMP7促进肝硬化的发展。巴塞尔S. Karger股份有限公司版权所有
Background/Aims: New strategies for the prevention and treatment of cirrhosis are urgently needed for improving therapeutic outcome. A role of microRNAs (miRNAs) in the pathogenesis of cirrhosis has been recently acknowledged, whereas the exact involved miRNAs as well as the associated molecular signaling pathways have not been determined. Specifically, the studies on the relationship between miR-22 and bone morphogenic protein 7 (BMP7) in the development of cirrhosis are lacking. Methods: We examined the correlation of the levels of miR-22 and bone morphogenic protein 7 (BMP7) in the liver biopsies from patients with cirrhosis. We examined overexpression or suppression of miR-22 on BMP7 in hepatocytes. We examined the binding of miR-22 to the 3'-UTR of BMP7 mRNA. Finally, in a carbon tetrachloride (CCl4)-induced cirrhosis model in mice, we gave mice adeno-associated viruses carrying antisense of miR-22, and examined its effects on BMP7 levels and the hallmarks of cirrhosis. Results: The levels of miR-22 and BMP7 in the liver biopsies from patients were strongly and inversely correlated. MiR-22 inhibited BMP7 expression in hepatocytes, through directly binding the 3'-UTR of BMP7 mRNA. Expression of antisense miR-22 significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl4, possibly through upregulation of BMP7. Conclusions: MiR-22 promotes the development of cirrhosis through BMP7 suppression. Copyright (C) 2015 S. Karger AG, Basel