PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury

作者：Yu Dun, Hanbing Hu, Fuli Liu, Yiru Shao, Daikun He, Lin Zhang, Jie Shen · 发表于：Biomedicine & Pharmacotherapy · 年份：2023 · DOI：10.1016/j.biopha.2023.114654 · 被引用次数：13 · 研究领域：Cancer, Hypoxia, and Metabolism、Angiogenesis and VEGF in Cancer、Neonatal Respiratory Health Research

Accidental exposure to phosgene can cause acute lung injury (ALI), characterized by uncontrolled inflammation and impaired lung blood-gas barrier. CD34+CD45+ cells with high pituitary tumor transforming gene 1 (PTTG1) expression were identified around rat pulmonary vessels through single-cell RNA sequencing, and have been shown to attenuate P-ALI by promoting lung vascular barrier repair. As a transcription factor closely related to angiogenesis, whether PTTG1 plays a role in CD34+CD45+ cell repairing the pulmonary vascular barrier in rats with P-ALI remains unclear. This study provided compelling evidence that CD34+CD45+ cells possess endothelial differentiation potential. Rats with P-ALI were intratracheally administered with CD34+CD45+ cells transfected with or without PTTG1-overexpressing and sh-PTTG1 lentivirus. It was found that CD34+CD45+ cells reduced the pulmonary vascular permeability and mitigated the lung inflammation, which could be reversed by knocking down PTTG1. Although PTTG1 overexpression enhanced the ability of CD34+CD45+ cells to attenuate P-ALI, no significant difference was found. PTTG1 was found to regulate the endothelial differentiation of CD34+CD45+ cells. In addition, knocking down of PTTG1 significantly reduced the protein levels of VEGF and bFGF, as well as their receptors, which in turn inhibited the activation of the PI3K/AKT/eNOS signaling pathway in CD34+CD45+ cells. Moreover, LY294002 (PI3K inhibitor) treatment inhibited the endothelial diff...