Abstract：
Apelin-13, a type of active peptide, can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the specific mechanism is unclear. Cell cycle checkpoint kinase 1 (Chk1) plays an important role in DNA damage. Here, we investigated the regulatory effect of Apelin on Chk1 in ALI. Chk1-knockout and -overexpression mice were used to explore the role of Chk1 in LPS-induced ALI mice treated with or without Apelin-13. In addition, A549 cells were also treated with LPS to establish a cell model. Chk1 knockdown inhibited the destruction of alveolar structure, the damage of lung epithelial barrier function, and DNA damage in the ALI mouse model. Conversely, Chk1 overexpression had the opposite effect. Furthermore, Apelin-13 reduced Chk1 expression and DNA damage to improve the impaired lung epithelial barrier function in the ALI model. However, the high expression of Chk1 attenuated the protective effect of Apelin-13 on ALI. Notably, Apelin-13 promoted Chk1 degradation through autophagy to regulate DNA damage in LPS-treated A549 cells. In summary, Apelin-13 regulates the expression of Chk1 by promoting autophagy, thereby inhibiting epithelial DNA damage and repairing epithelial barrier function.
摘要：
Apelin-13是一种活性肽,可以减轻脂多糖（LPS）诱导的急性肺损伤（ALI）。然而,具体机制尚不清楚。细胞周期检查点激酶1(Chk1)在DNA损伤中起重要作用。这里,我们研究了Apelin对ALI中Chk1的调节作用。使用Chk1敲除和过表达小鼠来探索Chk1在用或不用Apelin-13处理的LPS诱导的ALI小鼠中的作用。此外,A549细胞也用LPS处置以树立细胞模子。Chk1敲除抑制肺泡结构的破坏,肺上皮屏障功能的损伤，和ALI小鼠模型中的DNA损伤。相反，Chk1过表达具有相反的作用。此外，Apelin-13在ALI模型中降低Chk1表达和DNA损伤以改善受损的肺上皮屏障功能。然而,Chk1的高表达减弱了Apelin-13对ALI的保护作用。值得注意的是,Apelin-13通过自噬调节LPS处理的A549细胞DNA损伤促进Chk1降解。总之,Apelin-13通过促进自噬调节Chk1的表达,从而抑制上皮DNA损伤和修复上皮屏障功能。
