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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kostoulas G,Lang A,Nagase H,Baici A

doi

10.1016/s0014-5793(99)00897-2

keywords:

subject

Has Abstract

pub_date

1999-07-23 00:00:00

pages

286-90

issue

3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(99)00897-2

journal_volume

455

pub_type

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