Inhibition of human dermal fibroblast proliferation by removal of dermatan sulfate.
In the current study, a glycosaminoglycan lyase, chondroitinase B, was used to study the role of dermatan sulfate proteoglycans on human dermal fibroblast proliferation. Pretreatment with chondroitinase B significantly decreased fibroblast proliferative responses to serum (20% to 55%). In contrast, heparinase III and chondroitinase AC were less effective in inhibiting fibroblast proliferation to serum. Analysis of glycosaminoglycans on chondroitinase B-treated fibroblasts confirmed that dermatan sulfate was removed from fibroblasts by this enzyme. Chondroitinase B treatment also decreased proliferation to basic fibroblast growth factor (bFGF) by 20% and reduced receptor binding by 25%. Heparinase III inhibited bFGF binding by 73%, but decreased proliferation to bFGF by only 21%. Chondroitinase AC had no effect on bFGF proliferation or binding. These data suggest that dermatan sulfate proteoglycans play a significant role in the control of human dermal fibroblast proliferation.
Denholm
E M
EM
Department of Cellular Biology, IBEX Pharmaceuticals, Inc., 5485 Pare, H4P 1P7, Montreal, Quebec, Canada. edenholm@ibexpharma.com
Cauchon
E
E
Poulin
C
C
Silver
P J
PJ
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002808:Chondroitin Lyases / Q000494:pharmacology; D011508:Chondroitin Sulfate Proteoglycans / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D003871:Dermatan Sulfate / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011133:Polysaccharide-Lyases / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D011508:Chondroitin Sulfate Proteoglycans; C032649:dermatan sulfate proteoglycan; D016222:Fibroblast Growth Factor 2; D003871:Dermatan Sulfate; D002808:Chondroitin Lyases; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase