Tat-P combined with GAPR1 releases Beclin1 to promote autophagy and improve Bronchopulmonary dysplasia model
Yahui Zhou,
Yuting Zhu,
Weilai Jin,
Ru Yan,
Yuanyuan Fang,
Fan Zhang,
Tonghui Tang,
Si Chen,
Jing Chen,
Fan Zhang,
Zhangbin Yu,
Le Zang,
Zhiwei Yu
Affiliations
Yahui Zhou
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China; Corresponding author
Yuting Zhu
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Weilai Jin
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Ru Yan
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Yuanyuan Fang
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Fan Zhang
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Tonghui Tang
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Si Chen
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Jing Chen
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China
Fan Zhang
Department of Pediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China
Zhangbin Yu
Department of Neonatology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China; Corresponding author
Le Zang
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China; Corresponding author
Zhiwei Yu
Department of Neonatology, Wuxi Children’s Hospital affiliated to Jiangnan University, Wuxi, China; Corresponding author
Summary: Long-term exposure to hyperoxia can leading to the bronchopulmonary dysplasia (BPD). The progression of BPD is primarily driven by the apoptosis of alveolar epithelial cells, and the regulation of autophagy has an impact on apoptosis. This study aims to investigate the therapeutic potential and underlying mechanism of an autophagy-promoting peptide (Tat-P) in ameliorating BPD. In vitro experiments demonstrated that Tat-P promoted autophagy and partially prevented apoptosis caused by exposure to hyperoxia. Further investigation into the mechanism revealed that Tat-P competitively binds to GAPR1, displacing the Beclin1 protein and thereby inhibiting the apoptosis. In vivo experiments conducted on Sprague-Dawley pups exposed to high oxygen levels demonstrated that Tat-P promoted autophagy and reduced apoptosis in lung tissues and ameliorated BPD-related phenotypes. Our findings elucidate the underlying mechanisms and effects of Tat-P in enhancing autophagy and preventing apoptosis. This study presents an approach for the prevention and treatment of BPD.
