Department of Pharmacy, Zhejiang Provincial People's Hospital, Hangzhou, China.
People's Hospital of Hangzhou Medical College, Hangzhou, China.
J Cell Mol Med. 2020 Mar;24(6):3678-3691. doi: 10.1111/jcmm.15067. Epub 2020 Feb 14.
The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β-catenin signalling. In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy.
本研究旨在探讨长链非编码 RNA 牛磺酸上调基因 1（TUG1）在心肌肥厚中的作用及其潜在机制。通过横主动脉缩窄（TAC）手术处理小鼠以诱导心肌肥厚，并用苯肾上腺素（PE）处理心肌细胞以诱导肥大表型。通过苏木精-伊红（HE）、麦胚凝集素（WGA）和免疫荧光（IF）染色观察形态学改变。实时 PCR、Western blot 和 IF 染色检测 RNA 和蛋白的表达。荧光素酶报告基因检测和 RNA 下拉实验验证相互作用。结果表明，TAC 手术处理的小鼠心脏和 PE 诱导的心肌细胞中 TUG1 表达上调。功能上，过表达 TUG1 可减轻体内和体外的心肌肥厚。机制上，TUG1 可作为 miR-34a 的海绵体和隔离物，增加 Dickkopf 1（DKK1）的水平，从而抑制 Wnt/β-catenin 信号通路的激活。总之，本研究报道了 TUG1 在心肌肥厚中的保护作用及其调控机制，并提示 TUG1 可能成为治疗心肌肥厚的新的分子靶点。
