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

Abstract

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.

Down‐regulation of exosomal miR‐200c derived from keratinocytes in vitiligo lesions suppresses melanogenesis

“…41 Some studies showed that the inhibition of miR-200c relieved the acute lung injury induced by H5N1 virus infection in vivo. 42 In skin diseases, Magenta et al implicated miR-200c was up-regulated in psoriasis, which was related to the disease severity. 43 Hence, we further explore the im- family, which encodes a transcription factor with a highly conserved high-mobility group (HMG) DNA-binding domain.…”

Reduced peripheral blood miR‑140 may be a biomarker for acute lung injury by targeting Toll‑like receptor4 (TLR4)

“…MiR-34a levels are significantly higher in the lungs of neonatal rats exposed to hyperoxia compared with normal controls and miR-34a suppression improves the pulmonary phenotype and bronchopulmonary dysplasia-associated pulmonary arterial hypertension (14). Furthermore, plasma miR-200c-3p levels are much higher in patients with severe pneumonia compared with healthy controls (15).…”

Non-coding RNAs in pneumonia diagnosis

“…Картина усложняется тем, что пневмонии могут развиваться вследствие вирусной или комбинированной инфекции. Было показано, что разные клеточные линии и даже разные типы легочного эпителия в ответ на инфекционные агенты экспрессируют разные наборы микроРНК [45,46]. Кроме типа клеток важно их микроокружение, так, на клеточной модели пневмонии после обработки ЛПС макрофагов изучали секрецию апоптотических телец и обнаружили в них изменение набора и количества микроРНК; при этом индуцировались miR-221 и miR-222.…”

“…Подобная картина с повышением экспрессии miR-200c-3p наблюдалась при обработке культуры клеток ЛПС, синтетической двуцепочечной РНК (аналогом вирусной геномной РНК) и липотейхоевой кислотой (компонентом клеточной стенки грамположительных бактерий). Совокупность полученных результатов указывает на то, что супрессия АСЕ2 является универсальным механизмом при инфекции разными патогенами [46].…”