非酒精性脂肪性肝炎(NASH)又称代谢性脂肪性肝炎,是病理变化与酒精性肝炎相似但无过量饮酒史的临床综合征,好发于中年特别是超重肥胖个体。非酒精性脂肪性肝炎与肥胖、胰岛素抵抗、2型糖尿病、高脂血症等代谢紊乱关系密切,其主要特征为肝细胞大泡性脂肪变伴肝细胞损伤和炎症,严重者可发展为肝硬化,尚无特殊治疗措施。武汉大学人民医院生命科学学院心内科李洪亮教授及其团队,在NASH的发病机理研究上取得重大突破,并探索出新的治疗靶点,将其研究成果“Hepatocyte TRAF 6 Aggravates Hepatic Inflammation and Fibrosis by Promoting Lys6-Linked Polyubiquitination of ASK 1”发表在肝脏病研究领域的著名期刊《Hepatology》(IF=14.079)上。 该团队的研究首次阐明了NASH发病机制中ASK1激活的分子和细胞机制。研究表明肝细胞中过度活化的ASK1是通过促进肝细胞衍生因子的产生而激活肝星状细胞(HSC)的有效诱导物;肿瘤坏死因子受体相关因子6(TRAF6)促进Lys6-连接的多聚泛素化和随后的ASK1活化,以触发肝细胞中强大的促炎和促纤维化因子的释放,并且反过来驱动HSC活化和肝细胞纤维化;动物实验同时也表明,饮食诱导的肝脏炎症和纤维化在TRAF6极低表达的Traf6 +/-小鼠中显著减弱,而肝脏TRAF6过表达加剧了这些异常。这些结果都表明,TRAF6对ASK1的Lys6-连接多聚泛素化代表了肝细胞中ASK1活化的新机制,并且是NASH中促炎和促纤维化反应的关键驱动力。因此,抑制ASK1的Lys6-连接的多泛素化可以作为NASH治疗的潜在靶标。
分子机制:TRAF6将ASK1的Lys6-连接泛素化促进硫氧还蛋白(Trx)与ASK1的N-末端二聚化的解离,导致肝细胞中ASK1-JNK1/2-p38信号传导级联的加强激活。
在研究中,来自云克隆的产品承接了部分关键指标的检测。最主要的细胞因子TNF- a和MCP-1检测全部来自于云克隆,分别为SEA133Mu(ELISA Kit for Tumor Necrosis Factor Alpha (TNFa))和SEA087Mu(ELISA Kit for Monocyte Chemotactic Protein 1 (MCP1))。云克隆产品以过硬的质量和品质得到了各大著名实验室的青睐,借以武汉大学人民医院生命科学学院平台为NASH的研究贡献了一份绵薄之力。
该篇文章中所检测指标,云克隆其他与之相关的产品和文献引用量: 肿瘤坏死因子α/Tumor Necrosis Factor Alpha (TNFa)
产品类型product type |
适用物种suitable species |
SCI文献总量total literature |
蛋白、抗体、ELISA试剂盒Protein/Antibody/ELISA Kit |
人、大鼠、小鼠、兔、猪、牛、鸡、羊、马 Human/Rat/Mouse/Rabbit/Pig/Cattle/Chick/Sheep/Horse |
458篇 |
文献节选:Literature Excerpts
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- Shi Y, Wang L, Niu Y, et al. Fungal Component Coating Enhances Titanium Implant‐Bone Integration[J]. Advanced Functional Materials, 2018: 1804483.(IF=13.325)
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- Liu Q, Tong D, Liu G, et al. Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration[J]. Clinical Cancer Research, 2018, 24(22): 5622-5634.(IF=10.199)
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单核细胞趋化蛋白1/Monocyte Chemotactic Protein 1 (MCP1)
产品类型product type |
适用物种suitable species |
SCI文献总量total literature |
蛋白、抗体、ELISA试剂盒Protein/Antibody/ELISA Kit |
人、大鼠、小鼠、兔、猪、牛、鸡、羊、马 Human/Rat/Mouse/Rabbit/Pig/Cattle/Chick/Sheep/Horse |
54篇 |
文献节选:Literature Excerpts
- Ji Y X, Huang Z, Yang X, et al. The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis[J]. Nature medicine, 2018, 24(2): 213.(IF=32.621)
- Van Der Vorst E, Theodorou K, Wu Y, et al. High density lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-kB/STAT1-IRF1 signaling[J]. Atherosclerosis, 2017, 263: e6.(IF=20.565)
- Yang Y, Cheng X, Tian W, et al. MRTF-A steers an epigenetic complex to activate endothelin-induced pro-inflammatory transcription in vascular smooth muscle cells[J]. Nucleic acids research, 2014, 42(16): 10460-10472.(IF=11.561)
- Liu Y, Ge X, Dou X, et al. Protein inhibitor of activated STAT 1 (PIAS1) protects against obesity-induced insulin resistance by inhibiting inflammation cascade in adipose tissue[J]. Diabetes, 2015: db150278.(IF=7.273)
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