College of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei Province, PR China.
Department of Personal Administration, Tangshan People's Hospital, Tangshan 063000, Hebei Province, PR China.
Microvasc Res. 2022 Jan;139:104231. doi: 10.1016/j.mvr.2021.104231. Epub 2021 Aug 2.
Preeclampsia (PE) is a pregnancy-specific disease that is associated with oxidative stress-induced endothelial dysfunction. Long noncoding RNAs (lncRNAs) are related to PE progression. The purpose is to study whether lncRNA taurine-upregulated gene 1 (TUG1) takes part in endothelial dysfunction in PE.
The placenta tissues were collected from PE patients and normal subjects. Human umbilical vein endothelial cells (HUVECs) were suffered from hypoxia-reoxygenation (H/R). TUG1, miR-29a-3p and vascular endothelial growth factor A (VEGFA) were detected via qRT-PCR. soluble fms-related tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG) levels were detected by ELISA. Cell proliferation, migration, invasion and angiogenesis were examined via MTT, wound healing analysis, transwell and tube formation analysis. The proteins in VEGFA and angiopoietin 2 (Ang2)/tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) signaling were measured by western blot. The binding relationship was analyzed via Starbase, Jefferson and dual-luciferase reporter analysis.
TUG1 and VEGFA levels were downregulated, and levels of miR-29a-3p, sFLT1 and sENG were increased in PE patients. TUG1 abundance was reduced in H/R-stimulated HUVECs, and TUG1 overexpression increased proliferation, migration, invasion and angiogenesis, and activated the VEGFA and Ang2/Tie2 signaling in H/R-stimulated HUVECs. TUG1 sponged miR-29a-3p, and miR-29a-3p overexpression reversed the function of TUG1 on H/R-induced HUVECs dysfunction. MiR-29a-3p knockdown attenuated H/R-induced inhibition of proliferation, migration, invasion, angiogenesis and activation of the VEGFA and Ang2/Tie2 signaling in HUVECs. VEGFA and Ang2 were targeted by miR-29a-3p, and VEGFA or Ang2 silence weakened the role of miR-29a-3p knockdown in H/R-caused HUVECs dysfunction.
TUG1 facilitates proliferation, migration, invasion and angiogenesis in H/R-stimulated HUVECs via activating the VEGFA and Ang2/Tie2 signaling by regulating miR-29a-3p.
子痫前期（PE）是一种与氧化应激诱导的内皮功能障碍相关的妊娠特异性疾病。长链非编码 RNA（lncRNA）与 PE 的进展有关。本研究旨在探讨 lncRNA 牛磺酸上调基因 1（TUG1）是否参与 PE 中的内皮功能障碍。
收集 PE 患者和正常受试者的胎盘组织。人脐静脉内皮细胞（HUVEC）经历缺氧复氧（H/R）。通过 qRT-PCR 检测 TUG1、miR-29a-3p 和血管内皮生长因子 A（VEGFA）。通过 ELISA 检测可溶性 fms 相关酪氨酸激酶-1（sFLT1）和可溶性内皮糖蛋白（sENG）水平。通过 MTT、划痕愈合分析、Transwell 和管形成分析检测细胞增殖、迁移、侵袭和血管生成。通过 Western blot 检测 VEGFA 和血管生成素 2（Ang2）/含免疫球蛋白样和表皮生长因子样结构域 2（Tie2）信号的蛋白。通过 Starbase、Jefferson 和双荧光素酶报告分析分析结合关系。
PE 患者 TUG1 和 VEGFA 水平下调，miR-29a-3p、sFLT1 和 sENG 水平升高。H/R 刺激的 HUVEC 中 TUG1 丰度降低，TUG1 过表达增加增殖、迁移、侵袭和血管生成，并激活 H/R 刺激的 HUVEC 中的 VEGFA 和 Ang2/Tie2 信号。TUG1 海绵 miR-29a-3p，miR-29a-3p 过表达逆转了 TUG1 对 H/R 诱导的 HUVEC 功能障碍的作用。miR-29a-3p 敲低减弱了 H/R 诱导的 HUVEC 增殖、迁移、侵袭、血管生成和 VEGFA 和 Ang2/Tie2 信号激活。VEGFA 和 Ang2 是 miR-29a-3p 的靶点，VEGFA 或 Ang2 沉默减弱了 miR-29a-3p 敲低在 H/R 引起的 HUVEC 功能障碍中的作用。
TUG1 通过调节 miR-29a-3p 激活 VEGFA 和 Ang2/Tie2 信号通路，促进 H/R 刺激的 HUVEC 中的增殖、迁移、侵袭和血管生成。
