Two roles for transforming growth factor beta 1 in colon enterocytic cell differentiation.
Two roles for transforming growth factor beta 1 in colon enterocytic cell differentiation.
复制标题
转化生长因子β1在结肠肠细胞分化中的两种作用。
DOI：
--
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
E. Friedman
中科院分区：
文献类型：
--
作者：
M. Hafez;S. Hsu;Z. Yan;S. Winawer;E. Friedman
用双乙酰胺处理两个未分化的HT 29结肠癌亚系U4和U9，以上调它们的TGF-β 1 mRNA表达水平，来检测转化生长因子β 1（TGF-β 1）在肠细胞分化中的作用。虽然治疗后分泌的生物活性的TGF-β 1的两个线大致相同的水平，只有U4 H细胞被发现进行肠细胞分化时，培养postconfluence上胶原I包被transwell，形成极化单层细胞与顶端刷状缘，而U9 H细胞仍然是多层和未分化的。肠细胞U4 H细胞表现出四倍多的细胞表面表达的胶原蛋白I结合蛋白α 2-整联蛋白，两倍多的辅助胶原蛋白结合蛋白癌胚抗原，和几乎两倍多的结合到胶原蛋白I膜未分化的U9 H细胞。TGF-β 1治疗使U4细胞I型胶原结合加倍，α 2-整合素表达增加4倍，但癌胚抗原表达仅略微增加。U4 H细胞显示细胞周期的调节，可逆地阻止在G1期的限制点时，放置在汇合后培养条件下，启动肠细胞分化。与此相反，未分化的U9 H细胞表现出没有限制点，但在整个G1期被捕。TGF-β 1在G1期阻断了U4 H细胞的同步化，而它刺激了U9 H细胞的生长。因此，TGF-β 1在肠细胞分化中有两个作用：增加I型胶原粘附蛋白的水平和阻断G1期肠细胞，使其能够分化。
The role of transforming growth factor beta 1 (TGF-beta 1) in enterocytic differentiation was examined by treating two undifferentiated HT29 colon carcinoma sublines, U4 and U9, with hexamethylene bisacetamide to up-regulate their level of TGF-beta 1 mRNA expression. Although both lines after treatment secreted approximately equal levels of biologically active TGF-beta 1, only U4H cells were found to undergo enterocytic differentiation when cultured postconfluence on collagen I-coated transwells, forming polarized monolayer cells with an apical brush border, whereas U9H cells remained multilayered and undifferentiated. Enterocytic U4H cells exhibited four times as much cell surface expression of the collagen I-binding protein alpha 2-integrin, twice as much of the accessory collagen-binding protein carcinoembryonic antigen, and almost twice as much binding to collagen I films as undifferentiated U9H cells. TGF-beta 1 treatment doubled U4 cell collagen I binding, increased expression of alpha 2-integrin 4-fold, but increased carcinoembryonic antigen expression only marginally. U4H cells displayed cell cycle regulation by arresting reversibly at a restriction point in G1 when placed in the postconfluent culture conditions which initiated enterocytic differentiation. In contrast, undifferentiated U9H cells exhibited no restriction point but arrested throughout G1. TGF-beta 1 blocked synchronized U4H cells in G1, whereas it stimulated the growth of U9H cells. Thus, TGF-beta 1 has two roles in enterocytic differentiation: to increase levels of collagen I adhesion proteins and to block enterocytic cells in G1 so that they can differentiate.