南方医科大学学报2025，Vol.45Issue(11)：2475-2482,8.DOI:10.12122/j.issn.1673-4254.2025.11.20
沉默DDX17通过降低mTORC1活性抑制肺动脉平滑肌细胞的增殖和迁移
Silencing DDX17 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in vitro by decreasing mTORC1 activity
摘要
Abstract
Objective To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells(PASMCs)during the development of pulmonary hypertension(PH).Methods In murine PASMCs cultured under normoxic or hypoxic conditions,the effects of transfection with si-Ddx17 and insulin treatment,alone or in combination,on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining,scratch assay and Transwell assay.Western Blotting was performed to detect the changes in protein expression levels of DDX17,4EBP1,S6,p-4EBP1,and p-S6.In a mouse model of PH induced by intraperitoneal injection of monocrotaline(MCT),the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i.Results The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6,and these changes were obviously reversed by transfection with si-Ddx17.Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs.In the mouse model of MCT-induced PH,transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia.Conclusion The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice,and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.关键词
DDX17/肺动脉高压/肺动脉平滑肌细胞/增殖/迁移/mTORC1Key words
DDX17/pulmonary hypertension/pulmonary artery smooth muscle cells/proliferation/migration/mTORC1引用本文复制引用
邓湘湘,王嘉,熊迷,王挺,杨永健,李德,孙雄山..沉默DDX17通过降低mTORC1活性抑制肺动脉平滑肌细胞的增殖和迁移[J].南方医科大学学报,2025,45(11):2475-2482,8.基金项目
西部战区总医院星火创新人才项目基金(5156Z162) （5156Z162）
