Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. (2000 Jul)
differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease . background / AIMS : alterations in synthesis and breakdown of extracellular matrix components are known to play a crucial role in tissue remodelling during inflammation and wound healing . degradation of collagens is highly regulated by a cascade of matrix metalloproteinases ( MMPs ) . The current study was therefore designed to determine gene expression patterns of MMPs and their tissue inhibitors ( timps ) in single endoscopic biopsies of patients with inflammatory bowel disease ( IBD ) . patients / methods : mRNA expression was measured by quantitative competitive polymerase chain reaction ( PCR ) in biopsies from patients with ulcerative colitis ( n 21 ) and crohn s disease ( n 21 ) . protein expression was analysed by western blotting and immunohistochemistry . results : MMP 2 , MMP 14 , and TIMP 1 mrnas were marginally increased in inflamed , but 9 12 fold increased in ulcerated colonic mucosa in IBD whereas TIMP 2 mRNA expression remained unchanged . MMP 1 and MMP 3 mRNA expression correlated well with the histological degree of acute inflammation , resulting in more than 15 fold increased MMP 1 and MMP 3 mRNA levels in inflamed versus normal colon samples from patients with ulcerative colitis and crohn s disease . conclusion : profound overexpression of MMP 1 and MMP 3 mRNA transcripts suggests an important role for these enzymes in the …

Increased activity and expression of matrix metalloproteinase 9 in a rat model of distal colitis. (2002 Dec)
increased activity and expression of matrix metalloproteinase 9 in a rat model of distal colitis . matrix metalloproteinases may play a role in tissue remodelling and destruction associated with inflammation . We investigated activity and expression of matrix metalloproteinases in a rat model of colitis and tested the therapeutic potential of a synthetic inhibitor ( CGS 27023 A ) . colitis was induced by dextran sulphate sodium ( at 5 in drinking water for 5 days ) in a group of eight rats , whereas a matched control group received plain water . activity and expression of matrix metalloproteinases were measured in colonic tissue homogenates using zymography and western blot on days 3 and 5 after induction of colitis . In another set of experiments , two groups of colitic rats ( 20 per group ) were treated with CGS 27023 A ( 20 mg / kg ) or vehicle , respectively . On days 5 and 14 , colonic mucosal lesions were blindly scored by microscopic examination . induction of colitis led to a significant upregulation of matrix metalloproteinase 9 protein and its activity , but no change in matrix metalloproteinase 2 activity was observed . treatment with CGS 27023 A significantly decreased the extent and severity of epithelial injury but did not influence mucosal repair . We conclude that increased activity of matrix metalloproteinases may contribute to epithelial damage in this model of colitis .

Expression of matrix metalloproteinases 2 and 9 in intestinal tissue of patients with inflammatory bowel diseases. (2005 Jul)
expression of matrix metalloproteinases 2 and 9 in intestinal tissue of patients with inflammatory bowel diseases . background / AIMS : matrix metalloproteinases are major contributors in the breakdown and reconstitution of basement membranes and extracellular matrix in pathophysiological processes . We assessed the expression of matrix metalloproteinases 2 and 9 in intestinal tissue of patients with inflammatory bowel disease . patients / methods : resected tissue specimens from patients with crohn s disease or ulcerative colitis and control tissue from patients with a colorectal carcinoma were used for enzyme linked immunosorbent assay , zymography , activity assay , reverse transcription polymerase chain reaction and immunohistochemistry to evaluate the expression of these matrix metalloproteinases . results : matrix metalloproteinase 2 and more strongly matrix metalloproteinase 9 protein and mRNA were markedly increased in inflammatory bowel disease tissues , with the highest levels in severely inflamed tissues . immunohistochemistry showed that matrix metalloproteinase 2 was present in the extracellular matrix of the submucosa , with a lower but more generalised expression in the severely inflamed regions . matrix metalloproteinase 9 was most prominent in polymorphonuclear leukocytes and was increased , also in activity , in all inflammatory bowel disease tissues . An increased matrix metalloproteinase 9 expression in the extracellular matrix was observed in relation to the severity of inflammation . conclusions : matrix metalloproteinases 2 and 9 are enhanced in the intestinal tissue and seem to be actively involved in the inflammatory and remodelling processes in inflammatory bowel disease , …

Vascular smooth muscle cells and pericytes express MMP 1 , MMP 9 , TIMP 1 and type I procollagen in … (2001 Jul)
vascular smooth muscle cells and pericytes express MMP 1 , MMP 9 , TIMP 1 and type I procollagen in inflammatory bowel disease . AIMS : matrix metalloproteinases ( MMPs ) are involved in tissue remodelling , which is one of the important aspects of inflammatory disease . To assess the balance between the matrix degradation and production , we analysed the in situ expression of MMP 1 , 3 , 8 and 9 , tissue inhibitor of metalloproteinases ( TIMP ) 1 and 2 , and type I procollagen ( PC I ) in inflammatory bowel disease . methods and results : immunohistochemistry using frozen sections was performed in 17 patients with ulcerative colitis ( UC ) and 16 with crohn s disease ( CD ) . In both UC and CD , MMPs and timps were expressed by inflammatory cells as well as by fibroblastic cells most prominently in actively inflamed areas in ulcer bases , but sparsely in intact inflamed mucosa in both UC and CD . In UC , inflamed mucosa with erosions expressed these substances focally . fibroblasts also expressed PC I . We identified that vascular smooth muscle cells of venules in ulcer bases expressed MMP 1 and 9 , TIMP 1 and PC I . these venules also expressed E selectin , a cell adhesion molecule to facilitate the leucocyte extravasation , and vascular endothelial growth factor ( VEGF ) receptor 2 , consistent with their property of newly formed vessels . conclusions …

Increased mucosal matrix metalloproteinase 1 , 2 , 3 and 9 activity in patients with inflammatory bowel disease and the … (2007 Jul)
increased mucosal matrix metalloproteinase 1 , 2 , 3 and 9 activity in patients with inflammatory bowel disease and the relation with crohn s disease phenotype . background AND objective : matrix metalloproteinases are associated with matrix turnover in both physiological and pathological conditions . We postulate an association between aberrant matrix metalloproteinases proteolytic activity and the intestinal tissue destruction , seen in patients with crohn s disease and / or ulcerative colitis . materials AND methods : surgically resected inflamed and non inflamed ileum and colon with / without extensive fibrosis from 122 crohn s disease , 20 ulcerative colitis and 62 control patients were homogenized . protein levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases were measured by enzyme linked immunosorbent assays ( elisa ) , while matrix metalloproteinases and myeloperoxidase activity were measured by specific activity assays . results : expression of total levels of matrix metalloproteinases 1 , 2 , 3 and 9 relative to tissue inhibitor of metalloproteinases 1 and 2 was increased in inflamed inflammatory bowel disease compared to non inflamed inflammatory bowel disease and control intestinal mucosa . Also , net matrix metalloproteinases 1 , 2 , 3 and 9 activity in inflamed inflammatory bowel disease was increased , with similar expression profiles in crohn s disease and ulcerative colitis . within inflamed inflammatory bowel disease , a close correlation of matrix metalloproteinases with myeloperoxidase was observed . The expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases was similar in inflamed …