2. Academic Validation
  3. Apelin-13 improves pulmonary epithelial barrier function in a mouse model of LPS-induced acute lung injury by inhibiting Chk1-mediated DNA damage

Apelin-13 improves pulmonary epithelial barrier function in a mouse model of LPS-induced acute lung injury by inhibiting Chk1-mediated DNA damage

  • Biochem Pharmacol. 2024 May 25:116297. doi: 10.1016/j.bcp.2024.116297.
Siyue Chen 1,  Huihui Zhu 2,  Lidan Lin 3,  Liling Lu 4,  Lin Chen 1,  Luyao Zeng 2,  Wei Yue 2,  Xiaoxia Kong 5,  Hailin Zhang 6
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Children's Respiration disease, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China.
  • 3 School of Basic Medical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang 315302, PR China.
  • 4 Children's Hospital, Zhejiang University School of Medicine, Zhejiang 310000, PR China.
  • 5 School of Basic Medical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang 315302, PR China. Electronic address: kongxx@wmu.edu.cn.
  • 6 Department of Children's Respiration disease, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China. Electronic address: zhlwz97@hotmail.com.
PMID: 38801925 DOI: 10.1016/j.bcp.2024.116297
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.

Keywords

Acute lung injury; Apelin-13; Autophagy; Chk1; Epithelial barrier; P62.

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