Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.
As key components in the eukaryotic gene regulatory network, microRNAs (miRNAs) themselves are regulated at the level of both metabolism and activity. To identify factors that modulate miRNA activity, we used an Arabidopsis thaliana transgenic line expressing an artificial miRNA that causes trichome clustering and performed a screen for mutants with compromised miRNA activity (cma mutants) or enhanced miRNA activity (ema mutants). From this screen, we identified two novel mutant alleles of SERRATE, which is known to be required for miRNA biogenesis and dozens of other cma and ema mutants. In this study, we analyzed ema1. SAD2/EMA1 encodes an Importin b protein. The ema1 mutation had no effects on the accumulation of miRNAs and ARGONAUTE1 (AGO1) or on their cytoplasmic and nuclear distributions. Intriguingly, we found that the miRNA effector complexes purified from ema1 contained a larger amount of miRNAs and displayed elevated mRNA cleavage activities, indicating that EMA1 modulates miRNA activity by influencing the loading of miRNAs into AGO1 complexes. These results implicate EMA1 as a negative regulator of the miRNA pathway and reveal a novel layer of miRNA activity modulation.
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