Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases

FEBS Letters

Baici, Antonio²  Kostoulas, Georgios²  Lang, Angela²  Nagase, Hideaki¹ 

[1] Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA;University Hospital, Department of Rheumatology, CH-8091 Zurich, Switzerland

关键词: Human;    Osteoarthritis;    Articular cartilage;    Neoplasm;    Neovascularization;    Cathepsin B;    CAM;    (chick) chorioallantoic membrane;    CA-074;    N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline;    DMEM;    Dulbecco's modified Eagle's medium;    MALDI-TOF;    matrix-assisted laser desorption/ionization time-of-flight mass spectrometry;    MMP;    matrix metalloproteinase;    TIMP;    tissue inhibitor of matrix metalloproteinases;   

DOI  :  10.1016/S0014-5793(99)00897-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 chondrocytes 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.

【 授权许可】

Unknown