TUG1 Regulates Pulmonary Arterial Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension
| Autor: | Yingli Chen, Yan Xing, Shuang Wang, Hong-Xia Bao, Xiaowei Nie, Daling Zhu, Weiwei Cao, Shan Gao, Xiaodong Zheng |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Hypertension Pulmonary Cell Pulmonary Artery Vascular Remodeling 030204 cardiovascular system & hematology Muscle Smooth Vascular Vascular remodelling in the embryo Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Right ventricular hypertrophy Animals Humans Medicine Pulmonary Wedge Pressure 030212 general & internal medicine DAPI Viability assay Pulmonary wedge pressure Cells Cultured Cell Proliferation biology business.industry Cell growth medicine.disease Proliferating cell nuclear antigen Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Gene Expression Regulation chemistry biology.protein Cancer research RNA RNA Long Noncoding Cardiology and Cardiovascular Medicine business |
| Zdroj: | Canadian Journal of Cardiology. 35:1534-1545 |
| ISSN: | 0828-282X |
| Popis: | Background Pulmonary arterial hypertension (PAH) is a progressive disease, characterized by a persistent elevation of pulmonary arterial pressure and pulmonary vascular remodelling. Recent studies implicated that long noncoding RNAs (lncRNAs) play important roles in the development of various diseases. However, the underlying mechanisms of lncRNAs in PAH remain unclear. Here we show evidence for the modulation of human pulmonary smooth muscle cell (HPASMC) proliferation and vascular remodelling by lncRNA taurine upregulated gene1 (TUG1). Methods TUG1 expression and localization was detected by real-time polymerase chain reaction (PCR) and fluorescence in situ hybridization. Proliferation and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), western blot, bromodeoxyuridine incorporation, flow cytometry, scratch-wound assay, 4′,6-diamidino-2-phenylindole (DAPI), and caspase-3 activity. Luciferase activity and microscale thermophoresis were used to identify biomolecular interactions. The right ventricular systolic pressure and right ventricular hypertrophy were measured to evaluate cardiopulmonary function. Results TUG1 was upregulated in the pulmonary arteries of mice after a hypoxic assault and showed a significant increase in patients with PAH. TUG1 knockdown significantly prevented the development of PAH in vivo. Moreover, TUG1 promoted the proliferative responses of HPASMCs, including cell viability, 5-bromodeoxyuridine incorporation, the expression of proliferating cell nuclear antigen, and cell-cycle progression. All these functions of TUG1 were likely to be associated with miR-328. Conclusions The present study indicates that TUG1, a novel potential target for the treatment of PAH, is necessary for HPASMC proliferation and pulmonary vascular remodelling. |
| Databáze: | OpenAIRE |
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