Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases
Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases
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DOI：
10.1016/s0014-5793(99)00897-2
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发表时间：
1999-07-23
期刊：
影响因子：
3.5
通讯作者：
Baici, A
中科院分区：
文献类型：
--
作者：
Kostoulas, G;Lang, A;Baici, A
基质金属蛋白酶（MMPs）的组织抑制剂TIMP-1和TIMP-2也是血管生成抑制剂。组织蛋白酶B和MMPs存在于癌症和骨关节炎等疾病中新血管形成的部位。将TIMP-1、TIMP-2以及来自人关节软骨细胞的两种抑制剂与组织蛋白酶B混合使用，会导致它们碎裂，从而失去它们的mmp抑制和抗血管生成活性。我们的数据表明，除了直接参与组织破坏外，组织蛋白酶B还可能有害于另外两个原因：在缺乏上调这些酶的机制的情况下，它会提高MMPs的活性，并刺激血管生成。这是在各种病理情况下血管侵入的先决条件，其中癌症和骨关节炎是突出的例子，(C) 1999年欧洲生化学会联合会。
The tissue inhibitors of matrix metalloproteinases (MMPs), TIMP-1 and TIMP-2, are also angiogenesis inhibitors. Cathepsin B and MMPs are found at sites of neovascularization in pathologies such as cancer and osteoarthritis, Treatment of TIMP-1, TIMP-2, and of a mixture of both inhibitors from human articular chondricytes with cathepsin B resulted in their fragmentation, whereby they lost their MMP-inhibitory and anti-angiogenic activities. Our data suggest that, besides directly participating in tissue destruction, cathepsin B can be harmful for two further reasons: it raises the activity of the MMPs also in the absence of mechanisms up-regulating these enzymes, and it stimulates angiogenesis. This is a prerequisite for blood vessel invasion in a variety of pathological situations of which cancer and osteoarthritis are prominent examples, (C) 1999 Federation of European Biochemical Societies.