Silencing DDX17 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in vitro by decreasing mTORC1 activity.
10.12122/j.issn.1673-4254.2025.11.20
- Author:
Xiangxiang DENG
1
;
Jia WANG
2
;
Mi XIONG
1
;
Ting WANG
2
;
Yongjian YANG
2
;
De LI
2
;
Xiongshan SUN
1
Author Information
1. Department of Cardiovascular Medicine, School of Clinical Medicine, Southwest Medical University, Luzhou 646000, China.
2. Department of Cardiology, Western Theater Command General Hospital, Chengdu 610083, China.
- Publication Type:Journal Article
- Keywords:
DDX17;
mTORC1;
migration;
proliferation;
pulmonary artery smooth muscle cells;
pulmonary hypertension
- MeSH:
Animals;
Cell Proliferation;
Cell Movement;
DEAD-box RNA Helicases/metabolism*;
Myocytes, Smooth Muscle/metabolism*;
Mice;
Pulmonary Artery/cytology*;
Hypertension, Pulmonary/metabolism*;
Mechanistic Target of Rapamycin Complex 1;
Cells, Cultured;
Muscle, Smooth, Vascular/cytology*
- From:
Journal of Southern Medical University
2025;45(11):2475-2482
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES: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.
CONCLUSIONS: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.
