长链非编码 RNA CASC2 抑制低氧诱导的肺动脉高压中的肺动脉平滑肌细胞增殖和表型转换。
Long non-coding RNA CASC2 suppresses pulmonary artery smooth muscle cell proliferation and phenotypic switch in hypoxia-induced pulmonary hypertension.
机构信息
Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.167 Beilishi Rd., Xicheng District, Beijing, 100037, China.
Surgical Intensive Care Unit, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China.
出版信息
Respir Res. 2019 Mar 11;20(1):53. doi: 10.1186/s12931-019-1018-x.
BACKGROUND
In this study, we aimed to investigate whether and how lncRNA CASC2 was involved in hypoxia-induced pulmonary hypertension (PH)-related vascular remodeling.
METHODS
The 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.
RESULTS
The 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.
CONCLUSION
LncRNA CASC2 inhibited cell proliferation, migration and phenotypic switch of PASMCs to inhibit the vascular remodeling in hypoxia-induced PH.
背景
在这项研究中，我们旨在探讨长非编码 RNA CASC2 是否以及如何参与低氧诱导的肺动脉高压（PH）相关的血管重构。
方法
通过 qRT-PCR 检测 lncRNA 或 mRNA 的表达，通过 Western blot 分析或免疫组织化学检测蛋白表达。细胞计数和 EdU（5-乙炔基-2'-脱氧尿苷）染色用于评估细胞增殖。此外，还进行了流式细胞术和划痕愈合试验，分别评估细胞凋亡和细胞迁移。建立低氧诱导的 PH 大鼠模型并进行血流动力学测量。进行苏木精和伊红（HE）以及马松三色染色进行肺动脉形态计量学分析。
结果
lncRNA CASC2 在低氧诱导的大鼠肺动脉组织和肺动脉平滑肌细胞（PASMCs）中的表达降低。lncRNA CASC2 的上调抑制了低氧诱导的 PH 中体外和体内的细胞增殖、迁移，但增强了细胞凋亡。Western blot 分析和免疫组织化学显示，lncRNA CASC2 的上调极大地降低了低氧诱导的 PH 中表型转换相关标志物α-SMA 的表达。此外，通过肺动脉形态计量学分析表明，lncRNA CASC2 抑制了低氧诱导的大鼠肺动脉组织的血管重构。
结论
lncRNA CASC2 通过抑制 PASMCs 的增殖、迁移和表型转换，抑制低氧诱导的 PH 中的血管重构。
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