ABSTRACT

Acinetobacter baumanniitriggers autophagy, affects the degradation of autophagy, and causes severe inflammatory injury. LncRNA growth arrest-specific transcript 5 (LncRNA-GAS5) and Yin and Yang 1 (YY1) are known to play an important role in the regulation of autophagy, however, the precise role of LncRNA-GAS5 and YY1 in the damage to autophagy caused by Acinetobacter baumanniiremains unclear. The aim of this study was to investigate the role of LncRNA-GAS5 and YY1 in the regulation of autophagy induced by Acinetobacter baumannii. We found that LncRNA-GAS5 was up-regulated following infection with Acinetobacter baumannii, thus resulting in the degradation of STX17, autophagy disorders, and the aggravated replication of Acinetobacter baumannii. We also analyzed the mechanism of interaction between LncRNA-GAS5 and YY1 and found that YY1 regulated its expression in a negative manner by binding to the promoter of LncRNA-GAS5. LncRNA-GAS5 and YY1 had opposite effects on the expression of STX17, this process maintained the stable expression of STX17. Following Acinetobacter baumannii infection, YY1 was down regulated and then separated from the binding region of LncRNA-GAS5, thus resulting in the activation of LncRNA-GAS5 transcription and reduction in STX17 protein expression. Finally, we infected LncRNA-GAS5 knockdown mice with Acinetobacter baumannii, the expression levels of IFN-β in the lungs increased significantly, this alleviated lung injury. In conclusion, our work demonstrated the mechanism by which Acinetobacter baumannii infection can cause the degradation of STX17. We also demonstrated that LncRNA-GAS5 may be a potential therapeutic target for the treatment of lung injury induced by Acinetobacter baumannii.

摘要

鲍曼不动杆菌引发自噬，影响自噬降解，造成严重的炎症损伤。已知 LncRNA 生长停滞特异性转录本 5 (LncRNA-GAS5) 和阴阳 1 (YY1) 在自噬调节中起重要作用，然而，LncRNA-GAS5 和 YY1 在自噬损伤中的确切作用引起鲍曼不动杆菌仍不清楚。本研究旨在探讨LncRNA-GAS5和YY1在调节鲍曼不动杆菌诱导的自噬中的作用。我们发现 LncRNA-GAS5 在感染鲍曼不动杆菌后上调，从而导致 STX17 降解、自噬障碍和鲍曼不动杆菌。我们还分析了LncRNA-GAS5与YY1相互作用的机制，发现YY1通过与LncRNA-GAS5的启动子结合，以负向调控其表达。LncRNA-GAS5和YY1对STX17的表达有相反的作用，这个过程维持了STX17的稳定表达。鲍曼不动杆菌感染后，YY1 被下调，然后从 LncRNA-GAS5 的结合区域分离，从而导致 LncRNA-GAS5 转录的激活和 STX17 蛋白表达的减少。最后，我们用鲍曼不动杆菌感染了 LncRNA-GAS5 敲低小鼠, 肺中 IFN-β 的表达水平显着增加, 从而减轻了肺损伤。总之，我们的工作证明了鲍曼不动杆菌感染导致 STX17 降解的机制。我们还证明了 LncRNA-GAS5 可能是治疗鲍曼不动杆菌引起的肺损伤的潜在治疗靶点。