Title: On the roles of extracellular matrix remodeling by gelatinase B
Authors: Opdenakker, Ghislain # ×
Issue Date: Jan-1997
Series Title: Verhandelingen - Koninklijke Academie voor Geneeskunde van België vol:59 issue:6 pages:489-514
Abstract: Human extracellular matrix is constantly remodelled by de novo synthesis of structural components and by degradation of the matrix proteins by various proteinases. The secreted proteolytic enzymes are regulated at several levels: by control of gene transcription, by glycosylation, by specific inhibitors and by enzyme activation processes. The latter level most often involves clipping of a proenzyme or zymogen into an active proteinase. A series of such activation reactions leads to enzyme cascades. Whereas proteolytic activation is an all-or-none phenomenon, glycosylation usually has a restricted or fine-tuning effect on the catalytic activity of enzymes. Commonly, a two- to threefold reduction in specific activity is imposed by N-glycosylation on each member of the multi-enzyme chain. In a series comprising e.g. four enzymes, this can lead to significant influences (2(4)-3(4)-fold increase) on the substrate converting activity of the terminal member of a cascade. Gelatinase B is a terminal member of the protease cascade which leads to matrix degradation. It cleaves gelatins (denatured collagens or collagen fragments after digestion by collagenase) and other substrates and is thought to be involved in matrix remodeling during the normal processes of embryogenesis, tissue remodeling and development. Gelatinase B expression is upregulated in pathological states such as invasion of cancer cells and when leukocytes are released from the bone marrow and migrate towards an inflammatory focus. Proteases, including gelatinase B, are transcriptionally regulated by cytokines and directly by the activation processes. The gene regulation of enzyme inhibitors as well as other humoral factors, which contribute to protease activation, influence protease activities in an indirect way. Proteases might also play a role in the pathophysiology of chronic inflammation and autoimmunity by cleaving extracellular structural proteins and by generating proteolytic fragments. Indeed, these remnant fragments antigenically resemble the original precursor proteins, but are structurally and quantitatively different and may provoke an autoimmune response. Application of the knowledge of the structure, function and regulation of gelatinase B has contributed to the understanding of the mechanism of action of some gelatinase-inhibiting antirheumatic drugs and promises to contribute further to the development of novel treatment strategies for autoimmune diseases such as multiple sclerosis and for invasive cancers.
ISSN: 0302-6469
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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