Exploring the interface between metallo-proteinase activity and growth factor and cytokine bioavailability.
Metallo-proteinases are implicated in many processes involved in tissue remodeling, cell motility, morphogenesis, and cell and organ growth and differentiation. Recent data suggest that several members of the metzincin family including the matrix metallo-proteinases (MMPs), adamalysin-related proteinases, and the newly described pappalysins, are intimately involved in the activation and/or release of cytokines and growth factors. We review how metzincins, working through unique mechanisms, influence the extracellular milieu of several important cytokines and growth factors including transforming growth factor-beta (TGF-beta), TNF-alpha, IGFs and HB-epidermal growth factor (EGF). Because metzincins can modulate the bioavailability of these peptides, they may serve as unique target molecules to control cytokine and growth factor action in the extracellular environment.
Fowlkes
John L
JL
Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, 800 Marshal Street, Slot 900, Little Rock, AR 72202, USA. fowlkesjohnl@uams.edu
Winkler
Margaret K
MK
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism / Q000494:pharmacology*; D008954:Models, Biological; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D006133:Growth Substances; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein