Silencing DDX17 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in vitro by decreasing mTORC1 activity
DENG Xiangxiang
WANG Jia
XIONG Mi
WANG Ting
YANG Yongjian
LI De
SUN Xiongshan
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.
Keywords：DDX17pulmonary hypertensionpulmonary artery smooth muscle cellsproliferationmigrationmTORC1
Publication Date：2025-11-20
Online Publishing Date：2025-12-05(First online date of this platform, not the publication date of the document)
Pages：8( 2475-2482 )