Background: Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the vascular remodeling that also involves proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Overexpression of Storkhead box (STOX1) regulates genes involved hypoxia, redox balance, nitric oxide, and energy metabolism. In this study, we supposed Stox1 adjusted cells proliferation and migration in PASMCs development and played an important role in the pulmonary arterial vascular remodeling.
Methods: Hemodynamic assay and Right ventricular morphometric assay were used to check the rat model of PAH. HE staining was used to examine the arterial wall thickness. Masson staining showed that the deposition of collagen was significantly increased in PAH. In addition, Stox1 were assessed by immunofluorescence and immunohistochemistry staining. The effect of Stox1 on PASMCs was assessed by cell counting Kit-8 assay (CCK-8 assay), Scratch-Wound assay, EdU staining assay, Cell cycle analysis and Western blot.
Results: Right ventricular systolic pressure (RVSP) and right ventricular were significantly increased in hypoxia group and monocrotaline group compared to control group. The expression of Stox1 was increased in lung tissues in PAH rats. In vitro, the expression of Stox1 was up-regulated with time-dependent manner in hypoxia condition. Meanwhile, Stxo1 promoted the proliferation and migration in hypoxia-treated PASMCs. Moreover, we found that hypoxia promoted the expression of PCNA, Cyclin E and Cyclin A, increased more cells from G0/G1 phase to S phase and induced the activation of AKT proteins, which was significantly attenuated by inhibition of Stox1 expression in PASMCs.
Conclusion: These findings indicated that Stox1 induced proliferation of PASMCs and the effect is, at least in part, mediated through AKT signaling pathway.
Keywords: Hypoxia; Proliferation; Pulmonary artery hypertension; Stox1.
Copyright © 2019. Published by Elsevier Inc.