The lncRNA TUG1/miR-145-5p/FGF10 regulates proliferation and migration in VSMCs of hypertension.

Vascular remodeling is a characteristic pathological feature of hypertension, it can cause of increasing vascular resistance and decrease of compliance. Vascular smooth muscle cell (VSMCs) dysfunction is the important foundation of vascular remodeling. Increasing evidences have revealed that lncRNA is an important regulatory factor of VSMC function. In this paper, we explored the function of lncRNA TUG1 in vascular remodeling of hypertension. Here, we found that lncRNA TUG1 was highly expressed in aorta of spontaneously hypertensive rats (SHR) rats and promoted the proliferation and migration of VSMCs (SHR-VSMCs). Bioinformatics analyze showed that lncRNA TUG1 sequence had miR-145-5p binding sites. Luciferase reporter test, RNA pulldown and qRT-PCR showed that lncRNA TUG1 could bind miR-145-5p. Similarly, bioinformatics analyze found that FGF10 3 'UTR contained miR-145-5p binding sites. Luciferase reporter test, qRT-PCR and Western blot were shown that miR-145-5p inhibited FGF10 expression by binding to its 3 'UTR. MTT showed that miR-145-5p inhibited and FGF10 promoted SHR-VMSCs proliferation and migration. Overexpression of miR-145-5p or knocking down of FGF10 after overexpresion of lncRNA TUG1 could rescue the proliferation and migration promoted by lncRNA TUG1. LncRNA TUG1 and FGF10 promoted and miR-145-5p suppressed the expression of ß-catenin, TCF and LEF in SHR-VSMCs. Therefore, lncRNA TUG1/miR-145-5p/FGF10 promotes the proliferation and migration of VSMCs in hypertensive state by activating the Wnt/ß-catenin pathway.

Alleviation of Angiotensin II-Induced Vascular Endothelial Cell Injury through Long Non-coding RNA TUG1 Inhibition.

BACKGROUND: Hypertension damages endothelial cells, causing vascular remodelling. It is caused by Ang II-induced endothelial cell (EC) destruction. The long noncoding RNA (lncRNAs) are emerging regulators of endothelium homeostasis. Injured endothelium expresses lncRNA taurine-upregulated gene 1 (TUG1), which may mediate endothelial cell damage, proliferation, apoptosis, and autophagy and contribute to cardiovascular disease. However, uncertainty surrounds the function of lncRNA TUG1, on arterial endothelium cell damage. OBJECTIVE: This research aimed to investigate the role and mechanism of lncRNA TUG1 in vascular endothelial cell injury. METHOD: A microarray analysis of lncRNA human gene expression was used to identify differentially expressed lncRNAs in human umbilical vein endothelial cell (HUVEC) cultures. The viability, apoptosis, and migration of Ang II-treated HUVECs were then evaluated. In order to investigate the role of lncRNA TUG1 in hypertension, qRT-PCR, western blotting, and RNA-FISH were used to examine the expression of TUG1 in SHR mice. RESULTS: Ang II-activated HUVECs and SHR rats' abdominal aortas highly express the lncRNA TUG1. LncRNA TUG1 knockdown in HUVECs could increase cell viability, reduce apoptosis, and produce inflammatory factors. In SHR rat abdominal aortas, lncRNA TUG1 knockdown promoted proliferation and inhibited apoptosis. HE spotting showed that lncRNA TUG1 knockdown improved SHR rats' abdominal aorta shape. lncRNA TUG1 knockdown promotes miR-9- 5p, which inhibits CXCR4 following transcription. The lncRNA TUG1/miR-9-5p/CXCR4 axis and vascular cell injury were also examined. MiR-9-5p silencing or CXCR4 overexpression lowered cell survival, apoptosis, and lncRNA TUG1-induced IL-6 and NO expression. CONCLUSION: lncRNA TUG1 suppression could reduce Ang II-induced endothelial cell damage by regulating and targeting miR-9-5p to limit CXCR4 expression and open new vascular disease research pathways.

Associations of physical activity with cognitive function and daily physical function among Chinese individuals with heart disease: A cross-sectional study.

Background: To investigate the associations between different dimensions of physical activity (PA), cognitive function, and daily physical function in Chinese individuals with heart disease. Materials and methods: This study included 2,792 individuals from the China Health and Retirement Longitudinal Study conducted in 2015. Physical activity (PA) was divided into vigorous PA (VPA), moderate PA (MPA), and light PA (LPA). Linear and logistic regression models were established to assess the associations among the indicators. Results: Compared with taking no PA, MPA, and VPA at a frequency of 6-7 d/w had lower risks of impaired daily physical function (OR = 0.47, 95% CI: 0.25, 0.91; OR = 0.57, 95% CI: 0.37, 0.88) and higher cognitive function scores (ß = 1.22, 95% CI: 0.42, 2.03; ß = 1.08, 95% CI: 0.43, 1.73), while VPA at 3-5 d/w had lower cognitive function scores (ß = -1.96, 95% CI: -3.51, -0.40). Light PA (LPA) with a duration of 30-119 min/d had a lower risk of impaired daily physical function (OR = 0.59, 95% CI: 0.36, 0.97). Moderate PA (MPA) and VPA of 30-119 min/d had higher cognitive function scores (ß = 1.43, 95% CI: 0.49, 2.37; ß = 1.30, 95% CI: -0.56, 2.06). The 1,800-2,999 METs had the lowest risks of impaired daily physical function and the highest cognitive function scores (OR = 0.18, 95% CI: 0.04, 0.75; ß = 2.94, 95% CI: 1.67, 4.21). Conclusion: Moderate PA (MPA) and LPA with a frequency of 6-7 d/w and a duration of 30-119 min/d, and PA in 1,800-2,999 MET min/week were most closely related to better cognitive and daily physical function, while VPA (3-5 d/w; ≥300 min/w) may be related to low cognition, but high-quality research is necessary to prove causality. Trial registration: IRB00001052-11015.

Electroacupuncture alleviates orofacial allodynia and anxiety-like behaviors by regulating synaptic plasticity of the CA1 hippocampal region in a mouse model of trigeminal neuralgia.

Objective: Trigeminal neuralgia (TN), one of the most severe and debilitating chronic pain conditions, is often accompanied by mood disorders, such as anxiety and depression. Electroacupuncture (EA) is a characteristic therapy of Traditional Chinese Medicine with analgesic and anxiolytic effects. This study aimed to investigate whether EA ameliorates abnormal TN orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1. Materials and methods: A mouse infraorbital nerve transection model (pT-ION) of neuropathic pain was established, and EA or sham EA was used to treat ipsilateral acupuncture points (GV20-Baihui and ST7-Xiaguan). Golgi-Cox staining and transmission electron microscopy (TEM) were administrated to observe the changes of synaptic plasticity in the hippocampus CA1. Results: Stable and persistent orofacial allodynia and anxiety-like behaviors induced by pT-ION were related to changes in hippocampal synaptic plasticity. Golgi stainings showed a decrease in the density of dendritic spines, especially mushroom-type dendritic spines, in hippocampal CA1 neurons of pT-ION mice. TEM results showed that the density of synapses, membrane thickness of the postsynaptic density, and length of the synaptic active zone were decreased, whereas the width of the synaptic cleft was increased in pT-ION mice. EA attenuated pT-ION-induced orofacial allodynia and anxiety-like behaviors and effectively reversed the abnormal changes in dendritic spines and synapse of the hippocampal CA1 region. Conclusion: EA modulates synaptic plasticity of hippocampal CA1 neurons, thereby reducing abnormal orofacial pain and anxiety-like behavior. This provides evidence for a TN treatment strategy.