Department of Children's Respiration disease, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China; School of Basic Medical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang 315302, PR China.
Department of Children's Respiration disease, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China.
Biochem Pharmacol. 2024 Aug;226:116297. doi: 10.1016/j.bcp.2024.116297. Epub 2024 May 25.
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.
Apelin-13 是一种活性肽，可减轻脂多糖（LPS）诱导的急性肺损伤（ALI）。然而，其具体机制尚不清楚。细胞周期检查点激酶 1（Chk1）在 DNA 损伤中发挥重要作用。在这里，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讨 Chk1 在 LPS 诱导的 ALI 小鼠中的作用，这些小鼠经或未经 Apelin-13 处理。此外，还使用 LPS 处理 A549 细胞建立细胞模型。Chk1 敲低抑制了 ALI 小鼠模型中肺泡结构的破坏、肺上皮屏障功能的损伤和 DNA 损伤。相反，Chk1 过表达则产生相反的效果。此外，Apelin-13 降低 Chk1 表达和 DNA 损伤，改善 ALI 模型中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 通过自噬促进 Chk1 降解，从而调节 LPS 处理的 A549 细胞中的 DNA 损伤。总之，Apelin-13 通过促进自噬来调节 Chk1 的表达，从而抑制上皮细胞的 DNA 损伤并修复上皮屏障功能。
