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miRNA-200c-3p is crucial in acute respiratory distress syndrome

机译：miRNA-200c-3p在急性呼吸窘迫综合征中至关重要

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Influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ARDS), which is the most severe form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is a negative regulator of angiotensin II in the renin–angiotensin system, has been reported to have a crucial role in ALI. Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis. However, the molecular mechanism of the decreased expression of ACE2 in ALI is unclear. Here we show that avian influenza virus H5N1 induced the upregulation of miR-200c-3p, which was then demonstrated to target the 3′-untranslated region of ACE2. Then, we found that nonstructural protein 1 and viral RNA of H5N1 contributed to the induction of miR-200c-3p during viral infection. Additionally, the synthetic analog of viral double-stranded RNA (poly (I:C)), bacterial lipopolysaccharide and lipoteichoic acid can all markedly increase the expression of miR-200c-3p in a nuclear factor - κB-dependent manner. Furthermore, markedly elevated plasma levels of miR-200c-3p were observed in severe pneumonia patients. The inhibition of miR-200c-3p ameliorated the ALI induced by H5N1 virus infection in vivo , indicating a potential therapeutic target. Therefore, we identify a shared mechanism of viral and bacterial lung infection-induced ALI/ARDS via nuclear factor-κB-dependent upregulation of miR-200c-3p to reduce ACE2 levels, which leads increased angiotensin II levels and subsequently causes lung injury.
机译：众所周知，流感感染和肺炎可通过诱发急性呼吸窘迫综合征（ARDS）来导致其大量死亡，这是急性肺损伤（ALI）的最严重形式。据报道，血管紧张素转化酶2（ACE2）是肾素-血管紧张素系统中血管紧张素II的负调节剂，在ALI中起关键作用。 ACE2的下调始终与禽流感病毒，严重的急性呼吸综合征-冠状病毒，呼吸道合胞病毒和败血症诱导的ALI或ARDS相关。但是，尚不清楚ALI中ACE2表达降低的分子机制。在这里，我们显示禽流感病毒H5N1诱导了miR-200c-3p的上调，然后证明其靶向ACE2的3'-非翻译区。然后，我们发现非结构蛋白1和H5N1的病毒RNA有助于病毒感染期间miR-200c-3p的诱导。另外，病毒双链RNA（聚（I：C）），细菌脂多糖和脂蛋白酸的合成类似物都可以以核因子-κB依赖性方式显着增加miR-200c-3p的表达。此外，在严重的肺炎患者中观察到miR-200c-3p的血浆水平明显升高。对miR-200c-3p的抑制可改善体内H5N1病毒感染诱导的ALI，表明可能的治疗靶点。因此，我们通过miR-200c-3p的核因子-κB依赖性上调来降低ACE2水平，从而确定病毒和细菌性肺部感染诱导的ALI / ARDS的共享机制，从而降低ACE2水平，从而导致血管紧张素II水平升高，继而引起肺损伤。

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