β型转化生长因子信号通路的阻断可预防大鼠肝纤维化和肝功能障碍。
Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat.
作者信息
Qi Z, Atsuchi N, Ooshima A, Takeshita A, Ueno H
机构信息
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka 812-8582, Japan.
出版信息
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2345-9. doi: 10.1073/pnas.96.5.2345.
Abstract
We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCATbeta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis. In rats that received a single application of AdCATbeta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated. All AdCATbeta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCATbeta-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 be therapeutically useful.
摘要
我们通过腺病毒介导在经二甲基亚硝胺处理的大鼠肝脏中局部表达显性负性II型转化生长因子β（TGF-β）受体（AdCATβ-TR），消除了TGF-β信号传导，二甲基亚硝胺处理的大鼠是持续性肝纤维化模型。通过门静脉单次应用AdCATβ-TR的大鼠，经组织学和羟脯氨酸含量评估，肝纤维化明显减轻。所有接受AdCATβ-TR治疗的大鼠均存活，其血清透明质酸和转氨酶水平维持在低水平，而所有未接受AdCATβ-TR治疗的大鼠均死于肝功能障碍。结果表明，TGF-β在肝纤维化形成中确实起核心作用，并在持续性纤维化模型中明确显示，通过抗TGF-β干预预防纤维化可能具有治疗作用。
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Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2345-9. doi: 10.1073/pnas.96.5.2345.
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