Long non-coding RNA CASC2 suppresses pulmonary artery smooth muscle cell proliferation and phenotypic switch in hypoxia-induced pulmonary hypertension

Junsong Gong,Weili Zhang,Zujun Chen,Yu Chen,Haisong Lu,Lihuan Li,Fuxia Yan,Jia Shi,Huanran Lv

doi:10.1186/s12931-019-1018-x

Abstract

BackgroundIn this study, we aimed to investigate whether and how lncRNA CASC2 was involved in hypoxia-induced pulmonary hypertension (PH)-related vascular remodeling.MethodsThe expression of lncRNAs or mRNAs was detected by qRT-PCR, and western blot analysis or immunochemistry was employed for detecting the protein expression. Cell number assay and EdU (5-ethynyl-2′-deoxyuridine) staining were performed to assess cell proliferation. Besides, flow cytometry and wound healing assay were employed for assessments of cell apoptosis and cell migration, respectively. Rat model of hypoxic PH was established and the hemodynamic measurements were performed. Hematoxylin and eosin (HE) and Masson′s trichrome staining were carried out for pulmonary artery morphometric analysis.ResultsThe expression of lncRNA CASC2 was decreased in hypoxia-induced rat pulmonary arterial tissues and pulmonary artery smooth muscle cells (PASMCs). Up-regulation of lncRNA CASC2 inhibited cell proliferation, migration yet enhanced apoptosis in vitro and in vivo in hypoxia-induced PH. Western blot analysis and immunochemistry showed that up-regulation of lncRNA CASC2 greatly decreased the expression of phenotype switch-related marker α-SMA in hypoxia-induced PH. Furthermore, it was indicated by the pulmonary artery morphometric analysis that lncRNA CASC2 suppressed vascular remodeling of hypoxia-induced rat pulmonary arterial tissues.ConclusionLncRNA CASC2 inhibited cell proliferation, migration and phenotypic switch of PASMCs to inhibit the vascular remodeling in hypoxia-induced PH.

Highlights

Pulmonary hypertension (PH) is divided into pulmonary arterial hypertension (PAH), PH resulting from left heart disease, PH resulting from lung disease or hypoxia, chronic thromboembolic pulmonary hypertension and PH of uncertain multifactorial mechanism [1]
Up-regulation of Long non-coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2) inhibited proliferation, migration, while enhanced apoptosis in hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) Cell transfection was performed to modulate the expression of lncRNA CASC2 in PASMCs under both normoxic condition and hypoxia condition, and qRT-PCR was employed for detection of transfection efficiency in PASMCs
Relative expression of lncRNA CASC2 was significantly decreased in hypoxia group compared with normoxia group

Summary

Introduction

Pulmonary hypertension (PH) is divided into pulmonary arterial hypertension (PAH), PH resulting from left heart disease, PH resulting from lung disease or hypoxia, chronic thromboembolic pulmonary hypertension and PH of uncertain multifactorial mechanism [1]. PH is a vascular disease characterized by vasoconstriction, cellular hyperplasia, high pulmonary arterial pressure, right ventricular heart hypertrophy and vascular remodeling [2]. The abnormal proliferation and hypertrophy of pulmonary arterial smooth muscle cells (PASMCs) lead to vascular remodeling, which is a central process in the PH pathogenesis [4]. PASMCs underwent a contractile-to-synthetic phenotypic switch, which was accompanied with an excess of proliferation and a primary cause underlying vascular remodeling [6]. We aimed to investigate whether and how lncRNA CASC2 was involved in hypoxia-induced pulmonary hypertension (PH)-related vascular remodeling

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