Zhou Yahui, Zhu Yuting, Jin Weilai, Yan Ru, Fang Yuanyuan, Zhang Fan, Tang Tonghui, Chen Si, Chen Jing, Zhang Fan, Yu Zhangbin, Zang Le, Yu Zhiwei
Department of Neonatology, Wuxi Children's Hospital affiliated to Jiangnan University, Wuxi, China.
Department of Pediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.
iScience. 2023 Aug 2;26(9):107509. doi: 10.1016/j.isci.2023.107509. eCollection 2023 Sep 15.
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. 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. 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.
长期暴露于高氧环境会导致支气管肺发育不良（BPD）。BPD的进展主要由肺泡上皮细胞的凋亡驱动，而自噬的调节对凋亡有影响。本研究旨在探讨自噬促进肽（Tat-P）在改善BPD方面的治疗潜力及其潜在机制。实验表明，Tat-P促进自噬，并部分预防了高氧暴露引起的凋亡。对机制的进一步研究表明，Tat-P与GAPR1竞争性结合，取代Beclin1蛋白，从而抑制凋亡。在暴露于高氧水平的斯普拉格-道利幼崽身上进行的实验表明，Tat-P促进肺组织中的自噬并减少凋亡，并改善BPD相关表型。我们的研究结果阐明了Tat-P在增强自噬和预防凋亡方面的潜在机制和作用。本研究提出了一种预防和治疗BPD的方法。
