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首页> 外文学位 >Fetuin inhibits TGF-beta-stimulated collagen synthesis and protection from apoptosis in activated hepatic stellate cells.
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Fetuin inhibits TGF-beta-stimulated collagen synthesis and protection from apoptosis in activated hepatic stellate cells.

机译：胎球蛋白在活化的肝星状细胞中抑制TGF-β刺激的胶原蛋白合成并防止细胞凋亡。

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摘要

Liver fibrosis is a condition that is characterized by excessive synthesis and deposition of extracellular matrix (ECM) components in the liver. Activated hepatic stellate cells (HSCs) have been implicated as the principal producers of collagen, which is the main ECM protein increased in fibrosis. In a model of acute liver injury, these cells have been shown to undergo apoptosis during the activation process that subsequently leads to liver repair. However, there are several instances where activated HSCs avoid the apoptotic process, resulting in chronic liver conditions. The increased expression and secretion of TGF-β by activated HSCs in fibrosis is thought to be the major stimulus for the increased collagen synthesis and reduced apoptosis in activated HSCs. Our in vitro study showed that TGF-β1 significantly increased collagen synthesis in activated HSCs, and significantly reduced okadaic acid-induced apoptosis in the cells. Activated HSCs treated with fibrotic serum from a mouse model of fibrosis also displayed significantly lower levels of apoptosis than control, suggesting an increase of TGF-β in the serum. Fetuin, a serum glycoprotein, mimics the type II receptor for TGF-β, and therefore acts as an antagonist of the cytokine. We demonstrated that Fetuin significantly decreased exogenous TGF-β-stimulated collagen synthesis and TGF-β-inhibited apoptosis in activated HSCs, but did not affect endogenous TGF-β-inhibited apoptosis. These results suggest that TGF-β is involved in increasing collagen synthesis and reducing apoptosis in activated HSCs, however, it may not be the only cytokine involved in protecting activated HSCs from apoptosis. The antagonistic effect of Fetuin on TGF-β should be examined further and considered in future fibrosis therapy.
机译：肝纤维化是一种以肝脏中细胞外基质（ECM）成分过度合成和沉积为特征的疾病。活化的肝星状细胞（HSC）被认为是胶原蛋白的主要生产者，胶原蛋白是纤维化中增加的主要ECM蛋白。在急性肝损伤模型中，已显示这些细胞在激活过程中经历凋亡，随后导致肝修复。但是，在某些情况下，活化的HSC可以避免凋亡过程，从而导致慢性肝病。活化的HSCs在纤维化中TGF-β的表达和分泌增加被认为是活化的HSCs中胶原合成增加和细胞凋亡减少的主要刺激。我们的体外研究表明，TGF-β1显着增加了活化HSC中的胶原蛋白合成，并显着降低了冈田酸诱导的细胞凋亡。用来自纤维化小鼠模型的纤维化血清处理的活化的HSC也显示出比对照组低得多的凋亡水平，表明血清中TGF-β增加。胎球蛋白，一种血清糖蛋白，模仿TGF-β的II型受体，因此可作为细胞因子的拮抗剂。我们证明Fetuin显着降低了活化HSCs中外源TGF-β刺激的胶原蛋白合成和TGF-β抑制的细胞凋亡，但不影响内源性TGF-β抑制的细胞凋亡。这些结果表明，TGF-β参与增加活化的HSC中的胶原蛋白合成和减少细胞凋亡，然而，它可能不是唯一参与保护活化的HSCs免于凋亡的细胞因子。 Fetuin对TGF-β的拮抗作用应进一步研究，并在未来的纤维化治疗中予以考虑。

著录项

  • 作者

    Verma, Monica.;

  • 作者单位

    Dalhousie University (Canada).;

  • 授予单位 Dalhousie University (Canada).;
  • 学科 Health Sciences Pharmacology.
  • 学位 M.Sc.
  • 年度 2001
  • 页码 96 p.
  • 总页数 96
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

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