Blockade of type β transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat
Blockade of type β transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat
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DOI：
10.1073/pnas.96.5.2345
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Ueno, H
中科院分区：
文献类型：
--
作者：
Qi, Z;Atsuchi, N;Ueno, H
我们通过腺病毒介导的显性阴性II型TGF-β受体（AdCAT beta-TR）在二甲基亚硝胺治疗的大鼠（持续性肝纤维化模型）肝脏中的局部表达消除了β型转化生长因子（TGF-β）信号传导。在通过门静脉接受AdCAT β-TR单次应用的大鼠中，通过组织学和羟脯氨酸含量评估的肝纤维化显著减弱。所有AdCAT β-TR治疗的大鼠仍然活着，其血清透明质酸和转氨酶水平保持在低水平，而所有AdCAT β-TR未治疗的大鼠死于肝功能障碍。结果表明，TGF-β确实在肝纤维化发生中发挥核心作用，并清楚地表明在持续性纤维化模型中，通过抗TGF-β干预预防纤维化可能在治疗上有用。
We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCAT beta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis. In rats that received a single application of AdCAT beta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated. All AdCAT beta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCAT beta-TR-untreated rats died of liver dysfunction. The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearly in a persistent fibrosis model that prevention of fibrosis by anti-TGF-beta intervention could he therapeutically useful.