课题基金基金详情
miR-511调控HDGF介导的PI3K/AKT信号通路在汉黄芩素治疗低氧性肺动脉高压中的作用及机制研究
结题报告
批准号:
82003831
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
吴佩亮
依托单位:
学科分类:
消化与呼吸系统药物药理
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
吴佩亮
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中文摘要
寻找有效的防治肺动脉高压(PAH)的中药是重要的研究课题,如何诠释其科学内涵是中医药现代化亟待解决的关键问题之一。我们前期研究发现汉黄芩素可能通过调控PI3K/AKT信号通路抑制小鼠低氧性肺动脉高压。研究表明microRNAs及其信号途径在PAH发生发展过程具有重要的调节作用。结合文献及我们的前期研究,发现汉黄芩素可诱导低氧下肺动脉平滑肌细胞(PASMCs)miR-511的表达,且miR-511通过调控HDGF发挥其对PASMCs增殖和凋亡的影响,我们尝试建立miR-511/HDGF/PI3K/AKT信号通路的调控模式来充实PAH的发病机制。本研究拟从分子水平、组织水平和动物体内实验,明确汉黄芩素通过促进miR-511的表达,增强miR-511对HDGF的负调控,改变PI3K/AKT的磷酸化水平,进而减缓PAH的发生发展,该研究结果将丰富PAH的发病机制、为PAH治疗提供新靶点。
英文摘要
In recent years, Traditional Chinese Medicine (TCM) has made significant progress in modernization and globalization, however, the treatment of pulmonary arterial hypertension (PAH) is one of the key issues that need to be solved urgently in the medical field. Our pre-experiment research showed that wogonin may be capable of alleviating hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling by inhibiting the PI3K/AKT signaling pathway. MicroRNAs are small non-coding RNA molecules which participate in post-transcriptional gene regulation. It is found that microRNAs and their signaling pathways play an important regulatory role in the occurrence and development of PAH, and may be involved in the regulation of PAH pathogenesis. According to the literature and our previous studies, miR-511 expression was downregulated in pulmonary arterial smooth muscle cells under hypoxia and miR-511 can be promoted following wogonin treatment. Meanwhile, miR-511 may exert its moderator role on cell proliferation and apotosis by directly targeting HDGF. Herein, we attempted to establish the miR-511/HDGF/PI3K/AKT signaling pathway to enrich the theoretical basis for the pathogenesis and mechanism of PAH, thereby proposing novel approaches for the treatment of PAH. This project intends to investigate the regulatory effect of miR-511 and its underlying mechanism involved in the process of PAH with wogonin treatment. Future studies could also clarify the role of miR-511/HDGF/PI3K/AKT axis in hypoxia-induced pulmonary hypertension. This study will be helpful in finding a new TCM with good efficacy and providing novel therapeutic targets to treat pulmonary hypertension.
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DOI:10.1016/j.compbiomed.2022.105529
发表时间:2022-05-17
期刊:COMPUTERS IN BIOLOGY AND MEDICINE
影响因子:7.7
作者:Shi,Beibei;Zhou,Tao;Wu,Peiliang
通讯作者:Wu,Peiliang
DOI:10.1016/j.compbiomed.2023.107293
发表时间:2023-08-15
期刊:COMPUTERS IN BIOLOGY AND MEDICINE
影响因子:7.7
作者:Li,Yupeng;Fu,Yujie;Wu,Peiliang
通讯作者:Wu,Peiliang
DOI:10.1007/s42235-022-00292-z
发表时间:2023
期刊:JOURNAL OF BIONIC ENGINEERING
影响因子:4
作者:Hu, Jiao;Lv, Shushu;Zhou, Tao;Chen, Huiling;Xiao, Lei;Huang, Xiaoying;Wang, Liangxing;Wu, Peiliang
通讯作者:Wu, Peiliang
m6A 识别蛋白 IGF2BP2 通过增强 MARCKSL1 稳定性促进急性肺损伤的功能及机制研究
  • 批准号:
    LY22H010003
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2021
  • 负责人:
    吴佩亮
  • 依托单位:
国内基金
海外基金