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您现在的位置:首页 => 在线期刊 => 2020年 3期“药物性肝损伤的诊治与研究进展” => 其他肝病 =>转化生长因子β1信号..
转化生长因子β1信号通路对胚胎肝前体细胞分化的诱导作用
Effect of the transforming growth factor-β1 signaling pathway in inducing the differentiation of hepatic progenitor cells
文章发布日期:2020年03月19日  来源:  作者:玉苏甫卡迪尔·麦麦提尼加提,艾麦提·牙森,李文定,等  点击次数:207次  下载次数:70次

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【摘要】:目的 探讨TGFβ1对胚胎肝前体细胞(HPC)分化的影响。方法 体外培养HPC-E14.5细胞株并以细胞免疫荧光染色法鉴定。将细胞分为对照组(HPC)、HPC+TGFβ1组和HPC+SB431542组。HPC+TGFβ1组滴加外源性TGFβ1,HPC+SB431542组加入TGFβ1受体抑制剂SB431542,处理72 h后通过qRT-PCR法和Western Blot法分别检测AFP、Alb、细胞角蛋白19(CK19)mRNA及蛋白的表达情况;糖原染色法检测细胞分化后的功能。计量资料多组间比较采用单因素方差分析,进一步两两比较采用Dunnett’s t检验。结果 qRT-PCR检测结果:对照组的AFP mRNA表达量高于其他两组(F=128.937,P<0.01),HPC+TGFβ1组的CK19 mRNA表达量高于其他两组(F=414.467,P<0.01),HPC+SB431542组的Alb mRNA表达量最高(F=794.929,P<0.01)。Western Blot法检测结果:对照组的AFP蛋白表达量高于其他两组(F=269.000,P<0.01),HPC+TGFβ1组的CK19蛋白表达量高于其他两组(F=93.010,P<0.01),HPC+SB431542组的Alb蛋白表达水平均较其他两组明显升高(F=1086.000,P<0.01)。糖原染色法结果:对照组的糖原染色表达阳性面积比例小于其他两组(F=79.251,P<0.05)。结论 TGFβ1信号诱导HPC向有功能的胆管细胞分化,而阻断TGFβ1信号通路后HPC具有向成熟肝细胞分化的趋势,分化后的胆管细胞和肝细胞具有正常的糖原储存和合成功能,这些细胞可能能够参与代谢活动。
【Abstract】:Objective To investigate the effect of the transforming growth factor-β1 (TGF-β1) signaling pathway on the differentiation of hepatic progenitor cells (HPCs). Methods HPC-E14.5 cells were cultured in vitro and immunofluorescent staining was performed for identification. The cells were divided into control group (HPCs), HPCs+TGF-β1 group, and HPCs+SB431542 group. The cells in the HPCs+TGF-β1 group were treated with exogenous TGF-β1, and those in the HPCs+SB431542 group were treated with the TGF-β1 receptor inhibitor SB431542; after 72 hours of treatment, qRT-PCR and Western blot were used to measure the mRNA and protein expression of the stem cell marker alpha-fetoprotein (AFP), the hepatocyte marker albumin (Alb), and the cholangiocyte marker cytokeratin 19 (CK19), and periodic acid-Schiff staining was used to evaluate function after differentiation. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett’s t-test was used for further comparison between two groups. Results The results of qRT-PCR showed that the control group had significantly higher mRNA expression of AFP than the other two groups (F=128.937, P<0.01), the HPCs+TGF-β1 group had significantly higher mRNA expression of CK19 than the other two groups (F=414.467, P<0.01), and the HPCs+SB431542 group had the highest mRNA expression of Alb (F=794.929, P<0.01). The results of Western blot showed that the control group had significantly higher protein expression of AFP than the other two groups (F=269.000, P<0.01), the HPCs+TGF-β1 group had significantly higher protein expression of CK19 than the other two groups (F=93.010, P<0.01), and the HPCs+SB431542 group had significantly higher protein expression of Alb than the other two groups (F=1086.000, P<0.01). Periodic acid-Schiff staining showed that the control group had a significantly smaller positive staining area than the other two groups (F=79.251, P<0.05). Conclusion The TGF-β1 signaling pathway induces HPC differentiation into functional cholangiocytes; however, HPCs tend to differentiate into mature hepatocytes after the TGF-β1 signaling pathway is blocked. Such cholangiocytes and hepatocytes have the normal function of glycogen storage and synthesis and may participate in metabolic activities.
【关键字】:胚胎肝前体细胞; 转化生长因子β1; 细胞分化
【Key words】:fetal hepatic progenitor cells; transforming growth factor beta1; cell differentiation
【引证本文】:YUSUFUKADIER·MMTNJT, AIMAITI·YS, LI WD, et al. Effect of the transforming growth factor-β1 signaling pathway in inducing the differentiation of hepatic progenitor cells[J]. J Clin Hepatol, 2020, 36(3): 620-623. (in Chinese)
玉苏甫卡迪尔·麦麦提尼加提, 艾麦提·牙森, 李文定, 等. 转化生长因子β1信号通路对胚胎肝前体细胞分化的诱导作用[J]. 临床肝胆病杂志, 2020, 36(3): 620-623.

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