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OUYANG Shan, ZHANG Qinghua, QIAO Fuyuan
《医学前沿（英文）》 2007年 第1卷 第4期 页码 386-389 doi: 10.1007/s11684-007-0075-6
关键词： pregnancy concentration possible relationship responsible hepatocyte
Bioartificial liver devices: Perspectives on the state of the art
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《医学前沿（英文）》 2011年 第5卷 第1期 页码 15-19 doi: 10.1007/s11684-010-0110-x
Acute liver failure remains a significant cause of morbidity and mortality. Bioartificial liver (BAL) devices have been in development for more than 20 years. Such devices aim to temporarily take over the metabolic and excretory functions of the liver until the patients’ own liver has recovered or a donor liver becomes available for transplant. The important issues include the choice of cell materials and the design of the bioreactor. Ideal BAL cell materials should be of good viability and functionality, easy to access, and exclude immunoreactive and tumorigenic cell materials. Unfortunately, the current cells in use in BAL do not meet these requirements. One of the challenges in BAL development is the improvement of current materials; another key point concerning cell materials is the coculture of different cells. The bioreactor is an important component of BAL, because it determines the viability and function of the hepatocytes within it. From the perspective of bioengineering, a successful and clinically effective bioreactor should mimic the structure of the liver and provide an in vivo-like microenvironment for the growth of hepatocytes, thereby maintaining the cells’ viability and function to the maximum extent. One future trend in the development of the bioreactor is to improve the oxygen supply system. Another direction for future research on bioreactors is the application of biomedical materials. In conclusion, BAL is, in principle, an important therapeutic strategy for patients with acute liver failure, and may also be a bridge to liver transplantation. It requires further research and development, however, before it can enter clinical practice.
关键词： acute liver failure bioartificial livers hepatocyte bioreactor
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
《工程（英文）》 2024年 第32卷 第1期 页码 58-69 doi: 10.1016/j.eng.2023.09.019
Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells
时间序列多组学整合分析揭示原代肝细胞体外培养去分化过程伴随非降解性泛素化修饰的增加 Article
姜正一, 孙泽宇, 欧阳晓希, 赵亚磊, 周梦豪, 王保红, 李启睿, 范林骁, 张赛男, 李兰娟
《工程（英文）》 2020年 第6卷 第11期 页码 1302-1314 doi: 10.1016/j.eng.2020.02.011
目前，原代肝细胞（PHC）在各个研究领域被广泛使用，但是由于在体外培养过程中肝细胞特异性功能的迅速退化（即去分化），严重限制了它的应用范围。尽管学者已经对PHC的转录调控和全细胞蛋白质组（WCP）进行了广泛研究，但只有为数不多的研究考虑了蛋白质翻译后修饰（PTM）在这一过程中的作用。为了揭示引起PHC去分化的潜在机制，我们收集了在体外培养0 h、6 h、12 h、24 h和48 h的大鼠原代肝细胞样本，对各个时间点细胞样本的转录组、WCP、泛素化蛋白质组和磷酸化蛋白质组进行了定量分析。我们的数据包含了原代肝细胞体外培养去分化过程中详细的多组学分析结果，包括2196个蛋白质、2056个泛素化修饰位点和4932个磷酸化修饰位点。这项研究表明，PHC去分化过程中基因转录水平和蛋白质表达量之间的相关性较低。泛素化修饰组和对应的WCP联合分析表明，PHC去分化伴随着非降解性K27泛素化修饰位点的增加。对差异表达的磷酸化修饰蛋白进行功能富集分析，表明该过程中有铁死亡参与。其中，有404种蛋白质同时具有泛素化修饰位点和磷酸化修饰位点，被鉴定为与去分化事件有关的关键蛋白。最终，Ptbp1、Hnrpd、Hnrnpu和Srrm2被鉴定为PHC去分化过程中的hub分子。综上所述，我们的数据为抑制原代肝细胞体外培养去分化提供了潜在靶点分子及新的见解。
标题 作者 时间 类型 操作
Relationship between expression of hepatocyte grow factor and apoptosis of trophoblasts in hypertensive
OUYANG Shan, ZHANG Qinghua, QIAO Fuyuan
期刊论文
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
期刊论文
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