Expression of syndecan-1 in inflammatory bowel disease and a possible mechanism of heparin therapy.
Heparin apparently aids healing in ulcerative colitis although its mechanism of action is unknown. The purpose of this study was to investigate the hypothesis that heparin functions as a coreceptor molecule for basic fibroblast growth factor, a role usually performed by heparan sulfate chains on syndecan-1. A marked reduction of syndecan-1 immunostaining was found in reparative epithelium from inflammatory bowel disease patients. Removal of heparan sulfate on gastrointestinal epithelial cells in vitro reduced the proliferative response to basic fibroblast growth factor. The response to basic fibroblast growth factor was completely restored by the addition of heparin. Loss of syndecan-1 expression occurs in the regenerative mucosa in inflammatory bowel disease. Although this may facilitate tissue motility, its loss probably adversely affects the ability of cells to bind basic fibroblast growth factor. The present data show that heparin may substitute the loss of functional activity of syndecan-1 in the binding of basic fibroblast growth factor.
Day
R
R
Academic Department of Gastroenterology, ICRF Colorectal Cancer Unit, St Mark's Hospital, Harrow, UK.
Ilyas
M
M
Daszak
P
P
Talbot
I
I
Forbes
A
A
D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006497:Heparan Sulfate / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology; D007413:Intestinal Mucosa / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000032:analysis*; D011509:Proteoglycans / Q000032:analysis*; D053668:Syndecan-1; D053667:Syndecans
D016222:Fibroblast Growth Factor 2; D006493:Heparin; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; C508241:SDC1 protein, human