2. Academic Validation
  3. The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

  • Lab Invest. 2022 Aug;102(8):794-804. doi: 10.1038/s41374-022-00773-z.
Rui Jin  # 1 2,  Qianqian Gao  # 1,  Chunyu Yin  # 1,  Mengjia Zou 1,  Keyu Lu 1,  Wei Liu 3 4,  Yuting Zhu 5,  Mingshun Zhang 6 7,  Rui Cheng 8
Affiliations

Affiliations

  • 1 Department of Neonatal Medical Center, Children's Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Department of Neonatal Medical Center, Lianyungang Maternal and Child Health Hospital, Lianyungang, China.
  • 3 Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China.
  • 4 NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, China.
  • 5 Department of Neonatology, The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, China.
  • 6 Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China. mingshunzhang@njmu.edu.cn.
  • 7 NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, China. mingshunzhang@njmu.edu.cn.
  • 8 Department of Neonatal Medical Center, Children's Hospital of Nanjing Medical University, Nanjing, China. chengrui350@163.com.
  • # Contributed equally.
PMID: 35306530 DOI: 10.1038/s41374-022-00773-z
Abstract

Bronchopulmonary dysplasia (BPD) is the most common challenge in preterm neonates. Retardation of alveolar development characterizes the pulmonary pathology in BPD. In the present study, we explored the roles of the CD146-HIF-1α axis in BPD. We demonstrated that the levels of Reactive Oxygen Species (ROS) and soluble CD146 (sCD1146) were increased in the peripheral blood of preterm neonates with BPD. In alveolar epithelial cells, hyperoxia promoted the expression of HIF-1α and CD146, which reinforced each other. In a mouse model of BPD, by exposing pups to 65% hyperoxia, HIF-1α and CD146 were increased in the pulmonary tissues. Mechanistically, CD146 hindered the migration of alveolar epithelial cells; in contrast, movement was significantly enhanced in CD146-knockout alveolar epithelial cells. As expected, CD146-knockout ameliorated alveolarization and improved BPD disease severity. Taken together, our findings imply that the CD146-HIF-1α axis contributes to alveolarization and that CD146 may be a novel candidate in BPD therapy.

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