Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: can MMPs be good for you?
An abundance of literature over the past several years indicates a growing interest in the role of matrix metalloproteinases (MMPs) in normal physiology and in disease pathology. MMPs were originally defined by their ability to degrade the extracellular matrix, but it is now well documented that their substrates extend far beyond matrix components. Recent reviews discuss the structure and function of the MMP family members, as well as the promoter sequences that control gene expression. Thus, we focus on the signal transduction pathways that confer differential cell-type expression of MMPs, as well as on some novel non-matrix degrading functions of MMPs, particularly their intracellular location where they may contribute to apoptosis. In addition, increasing data implicate MMPs as "good guys", protective agents in some cancers and in helping to resolve acute pathologic conditions. Despite the intricate and complicated roles of MMPs in physiology and pathology, the goal of designing therapeutics that can selectively target MMPs remains a major focus. Developing MMP inhibitors with targeted specificity will be difficult; success will depend on understanding the role of these enzymes in homeostasis and on the careful delineation of mechanisms by which this family of enzymes mediates disease pathology.
Vincenti
Matthew P
MP
Department of Medicine, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA.
Brinckerhoff
Constance E
CE
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D016328:NF-kappa B; D050791:STAT Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases