α2-antiplasmin is involved in the growth factor β1 and fibrosis production of transforming
α2-antiplasmin is involved in the growth factor β1 and fibrosis production of transforming
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DOI：
10.1111/j.1538-7836.2007.02745.x
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发表时间：
2007-11-01
影响因子：
10.4
通讯作者：
Matsuno, H.
中科院分区：
文献类型：
--
作者：
Kanno, Y.;Kuroki, A.;Matsuno, H.
背景：纤维性疾病发生在大多数组织中。转化生长因子-β是肝纤维化的主要诱因。纤溶系统被认为在细胞外基质的降解中起着重要作用。然而，该系统如何影响纤维化的详细机制仍不清楚。方法和结果。我们检测了缺乏α(2)-抗纤溶酶(α2AP)的小鼠的实验性纤维化，α(2)-抗纤溶酶(α2AP)是一种有效和特异的纤溶酶抑制剂。我们发现，缺乏a2AP可减弱博莱霉素诱导的转化生长因子-β(1)的合成和纤维化。此外，与野生型小鼠相比，阿尔法(2)AP(-/-)小鼠移植的成纤维细胞产生的转化生长因子-β(1)显著减少。此外，我们还发现，α2AP特异性地诱导成纤维细胞产生转化生长因子-β(1)。结论：α2AP的缺乏抑制了转化生长因子-β(1)的合成，从而导致纤维化的减轻。这是第一个描述a2AP在纤维化过程中转化生长因子-β(1)合成中所起关键作用的报告。我们的结果为a2AP在纤维化中的作用提供了新的见解。
Background: Fibrotic disease occurs in most tissues. Transforming growth factor (TGF)-beta is the major inducer of fibrosis. The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices. However, the detailed mechanism of how this system affects fibrosis remains unclear. Methods and results. We examined experimental fibrosis in mice with a deficiency of alpha(2)-antiplasmin (alpha 2AP), which is a potent and specific plasmin inhibitor. We found that the lack of a2AP attenuated bleomycin-induced TGF-beta(1) synthesis and fibrosis. In addition, the production of TGF-beta(1) from the explanted fibroblasts of alpha(2)AP(-/-) mice decreased dramatically as compared to that in wild-type mice. Moreover, we found that alpha 2AP specifically induces the production of TGF-beta(1) in fibroblasts. Conclusion: The lack of alpha 2AP attenuated TGF-beta(1) synthesis, thereby resulting in attenuated fibrosis. This is the first report to describe the crucial role that a2AP plays in TGF-beta(1) synthesis during the process of fibrosis. Our results provide new insights into the role of a2AP in fibrosis.