Gb3通过激活脂滴蛋白HSD17B13促进非酒精性脂肪性肝炎的发生发展

批准号:
81900516
项目类别:
青年科学基金项目
资助金额:
21.0 万元
负责人:
李蓓
依托单位:
学科分类:
H0307.肝脏代谢障碍及相关疾病
结题年份:
2022
批准年份:
2019
项目状态:
已结题
项目参与者:
--
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中文摘要
非酒精性脂肪性肝炎(NASH)由于发病机制并不明确,目前尚无有效的治疗手段。前期研究发现Gb3贮积可导致肝脏脂代谢障碍和炎症细胞聚集。进一步研究提示,Gb3可激活脂滴蛋白HSD17B13,后者通过增强脂肪酸从头合成抑制脂肪酸β氧化,同时HSD17B13可促进白三烯B4生成,触发肝脏炎症反应。本项目基于课题组前期研究肝脏中Gb3蓄积可导致肝脏脂质沉积和炎症反应的研究方向,从细胞水平到动物水平,结合线粒体生物学、靶向代谢组学,13C-NMR同位素分析等多个研究层面和技术手段揭示Gb3贮积在NASH发生发展过程中的作用。阐明Gb3分别激活HSD17B13-ACC2途径和HSD17B13-5-LO-LTB4/BLT-1途径导致肝脏脂代谢障碍和炎症反应参与NASH的发生发展。本课题拟从代谢角度探究NASH发病机制,有望从源头找到导致NASH发病的诱因,为临床治疗提供新的思路及治疗靶点。
英文摘要
The pathogenesis of nonalcoholic fatty liver is not clear, and there is no effective treatment. Our pre-experiment have found that Gb3 storage can lead to liver lipid metabolism disorders and inflammatory cell aggregation. Further studies suggest that Gb3 can activate lipid droplet protein HSD17B13, which inhibits fatty acid β-oxidation by enhancing de novo lipogenesis, and HSD17B13 also promotes the formation of leukotriene B4 to trigger liver inflammation. This project is based on our previous research on the role of Gb3 accumulation in liver lipid deposition and inflammation. The study reveals the role of Gb3 storage in the development of NASH from cell level to animal level, combined with mitochondrial biology, targeted metabolomics and 13C-NMR isotope analysis and elucidates that Gb3 activates HSD17B13-ACC2 pathway and HSD17B13-5-LO-LTB4/BLT-1 pathway respectively, which lead to liver lipid metabolism disorders and inflammation in the development of NASH. This topic intends to explore the pathogenesis of NASH from the metabolic point of view. It is hopeful to find the cause of NASH from the source, and provide new ideas and therapeutic targets for clinical treatment.
非酒精性脂肪性肝炎(NASH)由于发病机制并不明确,目前尚无有效的治疗手段。前期研究发现GLA缺陷引起的Gb3贮积可导致肝脏脂代谢障碍和炎症细胞聚集。基于前期研究基础,本申请在动物水平及细胞水平分别构建了GLA缺陷模型,并予高脂刺激,发现GLA缺陷小鼠脂肪变更明显,炎症也更重;同样的,在细胞水平,高脂刺激导致细胞脂质沉积更明显,炎症因子水平更高;进一步地,机制研究发现GLA缺陷可激活HSD17β13-ACC2途径加重肝脏脂肪沉积。
期刊论文列表
专著列表
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会议论文列表
专利列表
DOI:000702360400003
发表时间:2021
期刊:Int J Clin Exp Med
影响因子:--
作者:Bei Li;Jiong Lu;Zhen You
通讯作者:Zhen You
Diagnostic Accuracy of Serum/Plasma Circular RNAs and the Combination of Circular RNAs and α-Fetoprotein for Detecting Hepatocellular Carcinoma: A Meta-Analysis.
血清/血浆环状 RNA 以及环状 RNA 与甲胎蛋白组合检测肝细胞癌的诊断准确性:荟萃分析
DOI:10.3389/fgene.2021.722208
发表时间:2021
期刊:Frontiers in genetics
影响因子:3.7
作者:Nie G;Peng D;Li B;Lu J;Cai Y;Xiong X;Cheng N
通讯作者:Cheng N
Laparoscopic liver resection for hepatocellular carcinoma presents less respiratory complications compared with open procedure: A propensity score analysis in the elderly
与开腹手术相比,腹腔镜肝切除术治疗肝细胞癌的呼吸系统并发症较少:老年人倾向评分分析
DOI:10.1016/j.ejso.2021.04.032
发表时间:2021-09-13
期刊:EJSO
影响因子:3.8
作者:Wen, Ningyuan;Liu, Fei;Cheng, Nansheng
通讯作者:Cheng, Nansheng
Gold-based nanoparticles realize photothermal and photodynamic synergistic treatment of liver cancer and improve the anaerobic tumor microenvironment under near-infrared light.
金基纳米粒子实现光热光动力协同治疗肝癌并改善近红外光下厌氧肿瘤微环境
DOI:10.3389/fbioe.2022.957349
发表时间:2022
期刊:FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
影响因子:5.7
作者:Li, Bei;Fu, Yi;Xie, Maodi;Feng, Lei;Niu, Xiaoya;Que, Lin;You, Zhen
通讯作者:You, Zhen
RNA sequencing reveals the long noncoding RNA and mRNA profiles and identifies long non-coding RNA TSPAN12 as a potential microvascular invasion-related biomarker in hepatocellular carcinoma
RNA 测序揭示了长非编码 RNA 和 mRNA 谱,并将长非编码 RNA TSPAN12 鉴定为肝细胞癌中潜在的微血管侵袭相关生物标志物
DOI:10.1016/j.biopha.2020.110111
发表时间:2020-06-01
期刊:BIOMEDICINE & PHARMACOTHERAPY
影响因子:7.5
作者:Lu, Jiong;Li, Bei;Cheng, Nansheng
通讯作者:Cheng, Nansheng
国内基金
海外基金
