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作 者:Changguo Wang Yingying Liu Weiyun Zhang Jian’an Huang Junhong Jiang Ran Wang Daxiong Zeng
机构地区:[1]Department of Pulmonary and Critical Care Medicine,the First Affiliated Hospital of Soochow University,Suzhou 215006,China [2]Department of Pulmonary and Critical Care Medicine,Suzhou Dushu Lake Hospital,Suzhou 215006,China [3]Department of Pulmonary and Critical Care Medicine,Dushu Lake Hospital Affiliated to Soochow University,Medical Center of Soochow University,Suzhou 215006,China [4]Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China
出 处:《Acta Biochimica et Biophysica Sinica》2023年第3期438-448,共11页生物化学与生物物理学报(英文版)
基 金:supported by the grants from the Suzhou Municipal Application Basic Research Project(SYS2019047);the Program of Key Talents of Medical Science in Jiangsu Province(QNRC2016745);the National Nature Science Foundation of China(No.81970051).
摘 要:Hypoxia plays a crucial role in pulmonary vascular remodelling at the early stage of chronic obstructive pulmonary disease(COPD).Circle RNA(circRNA)has been identified to play a critical role in multiple diseases.However,the role of circRNAs in pulmonary vascular remodelling in COPD remains unclear.In this study,we aim to investigate the role of circRNAs in pulmonary arterial smooth muscle cell proliferation and pulmonary vascular remodelling in COPD.COPD patients show lower partial pressure of arterial oxygen and pulmonary arterial remodeling as compared with controls.circRNA microarray and real-time PCR analyses show significantly higher level of circ-BPTF and lower miR-486-5p level in the pulmonary arteries of COPD patients as compared with controls.Hypoxia suppresses miR-486-5p expression but promotes expressions of circ-BPTF and cell migration inducing protein(CEMIP)in human pulmonary arterial smooth muscle cells(PASMCs)in vitro.Loss-and gain-of-function experiments show that circ-BPTF promotes PASMC proliferation in vitro.Moreover,luciferase reporter assay results indicate that circ-BPTF regulates PASMC proliferation by acting as an miR-486-5p sponge.CEMIP is identified as a candidate target gene of miR-486-5p by luciferase reporter assay.Overall,our study shows that circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promote hypoxic PASMC proliferation in pulmonary vascular remodelling in COPD.
关 键 词:pulmonary vascular remodelling hypoxia chronic obstructive pulmonary disease(COPD) circ-BPTF miR-486-5p CEMIP
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