Biological effects of hyaluronan in connective tissues, eye, skin, venous wall. Role in aging.
Hyaluronan, as most macromolecules of the extracellular matrix, are produced by the differentiated mesenchymal cells. These cells produce also enzymes degrading hyaluronan. This results in the presence of several hyaluronan pools of different molecular weights, all capable of interacting with surrounding cells, mediated by hyaluronan binding proteins and receptors. These interactions modulate cell phenotype and produce a variety of effects conditioning the specific functions of tissues. We shall discuss here several examples studied in our laboratory, concerning skin, cornea and the venous wall. Some of these actions might even be harmful, and could play an important role in aging of connective tissues with loss of function. Some of these age-dependent modifications mediated by hyaluronan will be reviewed and commented, especially the upregulation of matrix degrading enzymes as MMP-2 and MMP-9. We shall also mention some of our experiments for finding molecules capable of counteracting the harmful effects mediated by hyaluronan.
Robert
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Laboratoire de recherche ophtalmologique, hôpital Hôtel-Dieu, 1, place du Parvis-Notre-Dame, 75181 Paris cedex 04, France. lrobert5@wanadoo.fr
Robert
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Renard
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D003238:Connective Tissue / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D008322:Mammals; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014680:Veins / Q000378:metabolism*
C497483:CD44 protein, human; D006025:Glycosaminoglycans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; D010196:Pancreatic Elastase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9