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Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases
Author(s) -
Kostoulas Georgios,
Lang Angela,
Nagase Hideaki,
Baici Antonio
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00897-2
Subject(s) - angiogenesis , matrix metalloproteinase , neovascularization , cathepsin b , cancer research , cathepsin , matrix metalloproteinase inhibitor , chemistry , cathepsin d , enzyme , biology , biochemistry
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.