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KMID : 0381120220440040395
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Genes and Genomics
2022 Volume.44 No. 4 p.395 ~ p.404
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LncRNA-GAS5/miR-382-3p axis inhibits pulmonary artery remodeling and promotes autophagy in chronic thromboembolic pulmonary hypertension
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Feng Xiaona
Wang Kaifeng
Yang Ting
Liu Yanhui
Wang Xiaodong
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Abstract
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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.
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KEYWORD
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Chronic thromboembolic pulmonary hypertension, Long non-coding RNA GAS5, miR-382-3p, Autophagy
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