Regulation of elastase-type endopeptidase activity, MMP-2 and MMP-9 expression and activation in human dermal fibroblasts by fucose and a fucose-rich polysaccharide.
Tissue loss during ageing and age-dependent pathologies are the result of a disturbed regulation of proteolytic activities. Elastase-type endopeptidases, especially MMP-2 and -9, play an important role in this respect. Dermal fibroblast cultures and skin explant cultures were used in order to measure the efficiency of fucose and fucose-rich polysaccharides to downregulate the elastase-type endopeptidase activity. Fucose and fucose-rich polysaccharides were shown to downregulate this elastase-type activity, the basic activity and also the hyaluronan or kappa-elastin-stimulated activity. In skin explant cultures, we could demonstrate that fucose and fucose-rich polysaccharides produced an inhibition of the activation of the pro-form to the active form of MMP-9. Here, we show that mono-, di-, oligo- and polysaccharides acting on the elastin-laminin receptor and/or on the fucose-mannose receptor are efficient inhibitors of such enzymes by downregulating elastase-type endopeptidase activity, both at the level of their biosynthesis and at the level of the activation of the pro-enzymes. Fucose and fucose-rich polysaccharide preparations were shown to be efficient modulators of MMP-2 and MMP-9, activity with potential therapeutic applications in age-related pathologies accompanied by tissue loss.
Isnard
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Laboratoire de recherche en ophtalmologie, Hĵpital Hotel Dieu, Paris, France. n.isnard@extracellular-matrix.com
Péterszegi
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G
Robert
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AM
Robert
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L
D002675:Child, Preschool; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005643:Fucose / Q000494:pharmacology* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology* / Q000502:physiology
D061965:Matrix Metalloproteinase Inhibitors; D011134:Polysaccharides; D005643:Fucose; D010450:Endopeptidases; D010196:Pancreatic Elastase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9