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

doi:10.1016/j.isci.2023.107509

Tat-P combined with GAPR1 releases Beclin1 to promote autophagy and improve Bronchopulmonary dysplasia model

iScience. 2023 Aug 2;26(9):107509. doi: 10.1016/j.isci.2023.107509. eCollection 2023 Sep 15.

Authors

Yahui Zhou¹, Yuting Zhu¹, Weilai Jin¹, Ru Yan¹, Yuanyuan Fang¹, Fan Zhang¹, Tonghui Tang¹, Si Chen¹, Jing Chen¹, Fan Zhang², Zhangbin Yu^{3

4}, Le Zang¹, Zhiwei Yu¹

Affiliations

¹ Department of Neonatology, Wuxi Children's Hospital affiliated to Jiangnan University, Wuxi, China.
² Department of Pediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.
³ Department of Neonatology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China.
⁴ The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China.

Abstract

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.

Keywords: Biochemistry; Biological sciences; Cell biology; Molecular biology.