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

玉苏甫卡迪尔·麦麦提尼加提; 艾麦提·牙森; 李文定; 冉博; 吐尔干艾力·阿吉; 邵英梅; 温浩

doi:10.3969/j.issn.1001-5256.2020.03.030

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

DOI: 10.3969/j.issn.1001-5256.2020.03.030

1. 新疆医科大学“省部共建中亚高发病成因与防治”国家重点实验室
2. 新疆医科大学第一附属医院消化血管外科中心肝胆包虫外科

基金项目:

国家科技重大专项课题(2018ZX10301201)；新疆医科大学省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2017-1)；

详细信息

中图分类号: R329.2
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出版历程
- 收稿日期: 2019-10-17
- 出版日期: 2020-03-20

Effect of the transforming growth factor-β1 signaling pathway in inducing the differentiation of hepatic progenitor cells

State Key Laboratory of “Pathogenesis,Prevention,and Treatment of High Incidence Diseases in Central Asia”,Xinjiang Medical University

Research funding:

摘要

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 &...
- 胚胎肝前体细胞 /
- 转化生长因子β1 /
- 细胞分化
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.
- fetal hepatic progenitor cells /
- transforming growth factor beta1 /
- cell differentiation

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