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Transforming growth factor-β1 induces intestinal myofibroblast differentiation and modulates their migration

机译:转化生长因子-β1诱导肠道成肌纤维细胞分化并调节其迁移

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摘要

AIM: To investigate the effects of transforming growth factor β1 (TGF-β) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro.rnMETHODS: Primary CLPF cultures were incubated with TGF-pi and analyzed for production of a-smooth muscle actin (α-SMA), fibronectin (FN) and FN isoforms. Migration assays were performed in a modified 48-well Boyden chamber. Levels of total and phosphorylated focal adhesion kinase (FAK) in CLPF were analyzed after induction of migration.rnDid not change a-SMA levels, while TGF-pi treatment for 6 d significantly increased α-SMA production. Short, term incubation (6 h) with TGF-β1 enhanced CLPF migration, while long term treatment (6 d) of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1 (2 d) in contrast to long term incubation with TGF-β1 for 6 d. After induction of migration, TGF-pi-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells.rnCONCLUSION: Long term incubation of CLPF with TGF-β1 induced differentiation into myofibroblasts with enhanced α-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact (6 h) of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of α-SMA production.
机译:目的:探讨转化生长因子β1(TGF-β)对结肠固有层成纤维细胞(CLPF)向成肌纤维细胞分化的影响。方法:将原代CLPF培养物与TGF-pi一起孵育并分析α-生成平滑肌肌动蛋白(α-SMA),纤连蛋白(FN)和FN亚型。在改良的48孔Boyden腔室中进行迁移测定。诱导迁移后,分析CLPF中总的和磷酸化的粘着斑激酶(FAK)的水平。rn没有改变a-SMA的水平,而TGF-pi处理6天显着增加了α-SMA的产生。与未经处理的细胞相比,与TGF-β1短期孵育(6 h)可增强CLPF迁移,而与TGF-β1进行CLPF长期处理(6 d)可使迁移减少至15%-37%。与TGF-β1长期孵育6 d相比,TGF-β1短期孵育(2 d)后FN和FN亚型mRNA表达增加。诱导迁移后,与未处理的细胞相比,TGF-β1预孵育的CLPF显示出更高的FN及其同工型含量,总FAK和磷酸化的FAK含量较低。结论:长期与TGF-β1孵育的CLPF诱导分化为肌纤维母细胞,增强了α- SMA,降低了迁徙潜力和FAK磷酸化,并增加了FN的产生。相反,成纤维细胞与TGF-β1的短期接触(6小时)诱导了细胞迁移和FAK磷酸化的剂量依赖性增加,而没有诱导α-SMA的产生。

著录项

  • 来源
    《World Journal of Gastroenterology》 |2009年第12期|1431-1442|共12页
  • 作者单位

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany Department of Internal Medicine II, University of Jena, 07747 Jena, Germany;

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany;

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany;

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany;

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany;

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany;

    Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany Clinic of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zurich, 8091 Zurich, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    transforming growth factor β1; colonic fibroblasts; myofibroblasts; migration; fibronectin;

    机译:转化生长因子β1;结肠成纤维细胞肌成纤维细胞移民;纤连蛋白;

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