Abstract

Background We have clarified the role of miR-382-3p in chronic thromboembolic pulmonary hypertension (CTEPH), but what is less clear lies in its upstream regulatory mechanism. Objective To explore the regulation mechanism of GAS5/miR-382-3p axis on CTEPH. Methods In vitro, we constructed cell models by treating Pulmonary Artery Smooth Muscle Cells (PASMCs) with platelet-derived growth factor-BB (PDGF-BB). The effects of different concentrations of PDGF-BB on the activity of PASMCs were tested by cell counting kit-8 (CCK-8). The upstream lncRNA of miR-382-3p was screened and confirmed through bioinformatics analysis, RNA pull-down, quantitative reverse transcription polymerase chain reaction (qRT-PCR), dual luciferase reporter gene and RNA immunoprecipitation assays. The effects of GAS5/miR-382-3p axis on the viability, migration, and expressions of autophagy- and angiogenesis-related proteins were confirmed by rescue experiments (CCK-8, wound healing and western blot). In vivo, animal models by perfusing autologous blood vessels, the effects of GAS5 overexpression or silencing on the expressions of miR-382-3p, angiogenesis- and autophagy-related genes, mean pulmonary arterial pressure (mPAP) and pulmonary artery wall were determined by biological signal acquisition system, hematoxylin–eosin staining, qRT-PCR and western blot. Results PDGF-BB dose-dependently promoted PASMCs viability. XIST and GAS5 expressions in PASMCs were affected by the concentration of PDGF-BB, but only GAS5 can be pulled down by miR-382-3p probe. GAS5 targeted miR-382-3p to inhibit the viability and migration of PAMSCs, mPAP in CTEPH rats, pulmonary artery wall thickening and angiogenesis, and promote autophagy. Conclusions GAS5/miR-382-3p axis is involved in the regulation of pulmonary artery remodeling and autophagy in CTEPH.