| lncRNA Terc调控NLRP3对冠状动脉内皮细胞End-MT的影响 |
| 投稿时间：2025-01-15 修订日期：2025-03-07 点此下载全文 |
| 引用本文：王娟,祖力开尔·吐尔逊,郑丽华,吕忠英.lncRNA Terc调控NLRP3对冠状动脉内皮细胞End-MT的影响[J].医学研究杂志,2025,54(8):56-62, 87 |
| DOI：
10.11969/j.issn.1673-548X.2025.08.010 |
| 摘要点击次数: 16 |
| 全文下载次数: 9 |
|
| 基金项目:国家自然科学基金资助项目(81960052)；新疆维吾尔自治区自然科学基金资助项目(面上项目)(2022D01C325) |
|
| 中文摘要:目的 探究lncRNA Terc在人冠状动脉内皮细胞(human coronary artery endothelial cell,HCAEC)内皮间质转化(endothelial-mesenchymal transition,End-MT)中的功能及机制。方法 以转化生长因子-β(transforming growth factor-β,TGF-β)为诱导剂,构建HCAEC End-MT模型,并通过质粒转染敲低或过表达lncRNA Terc,或联合NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体抑制剂、核因子-κB(nuclear factor-κB,NF-κB)抑制剂干预细胞。采用CCK-8实验及Transwell实验检测细胞的增殖活力及迁移能力；酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测炎性细胞因子的表达差异；Western blot法检测纤维化相关蛋白及炎性小体标志蛋白的表达水平；实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction, RT-qPCR)法检测lncRNA Terc的表达水平。结果 lncRNA Terc在End-MT细胞模型中表达上调(P<0.01)；敲低lncRNA Terc后,HCAEC的增殖活力及迁移能力显著下降,α-平滑肌肌动蛋白(alpha-smooth muscle actin,α-SMA)、Ⅰ型胶原蛋白(Collagen Ⅰ)、NLRP3炎性小体标志蛋白表达、炎性细胞因子白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-18(interleukin-18,IL-18)表达也显著下调(P<0.01),而过表达lncRNA Terc的结果则与之相反；NLRP3炎性小体抑制剂可以削弱lncRNA Terc对End-MT的诱导作用；加入NF-κB抑制剂后,NLRP3、胱冬肽酶-1(caspase-1)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)、IL-1β、IL-18的蛋白表达水平显著下调(P<0.01)。结论 lncRNA Terc可以通过调控NF-κB/NLRP3通路促进HCAEC的End-MT。 |
| 中文关键词:心肌纤维化 内皮间质转化 lncRNA Terc NF-κB/NLRP3通路 |
| |
| LncRNA Terc Regulates the Effect of NLRP3 on Endothelium-mesenchymal Transition in Coronary Endothelial Cells. |
|
|
| Abstract:Objective To explore the function and mechanism of LncRNA Terc in endothelial-mesenchymal transition (End-MT) of human coronary artery endothelial cell (HCAEC). Methods The End-MT model of HCAEC was constructed by using transforming growth factor-β (TGF-β) as inducer, LncRNA Terc knockdown or overexpression plasmid transfected cells, or combined with NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome inhibitor, nuclear factor-κB (NF-κB) inhibitor intervention cells. The proliferation activity and migration ability of cells were detected by CCK-8 assay and Transwell assay. The expression of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of fibrosis-related proteins and inflammasome marker proteins were detected by Western blot. The expression level of lncRNA Terc was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Results LncRNA Terc was up-regulated in End-MT cell model (P<0.01). After knockdown of LncRNA Terc, the proliferation activity and migration ability of HCAEC were significantly decreased, and the expressions of alpha-smooth muscle actin (α-SMA), collagen Ⅰ and NLRP3 inflammatosomal marker proteins were significantly down-regulated, as well as the expressions of inflammatory factors IL-1β and IL-18 (P<0.01). However, the results after overexpression of lncRNA Terc were opposite. NLRP3 inflammasome inhibitors can weaken the induction effect of lncRNA Terc on End-MT. The addition of an NF-κB inhibitor resulted in a significantly down-regulation of NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), IL-1β and IL-18 (P<0.01). Conclusion LncRNA Terc can promote End-MT in HCAEC by regulating the NF-κB/NLRP3 pathway. |
| keywords:Myocardial fibrosis Endothelium-mesenchymal transition LncRNA Terc NF-κB/NLRP3 pathway |
| 查看全文 查看/发表评论 下载PDF阅读器 |
|
|
|
