Matrix metalloproteinases in inflammatory bowel disease : expression, regulation and clinical relevance

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Matrix metalloproteinases in inflammatory bowel disease : expression, regulation and clinical relevance

Type: Doctoral thesis
Title: Matrix metalloproteinases in inflammatory bowel disease : expression, regulation and clinical relevance
Author: Meijer, Martin Jan-Willem
Publisher: Department of Gastroenterology and Hepatology, Faculty of Medicine / Leiden University Medical Center (LUMC, Leiden University)
Issue Date: 2009-04-23
Keywords: Inflammatory Bowel Disease
Matrix Metalloproteinase
TNF-alpha
Abstract: Crohn’s disease (CD) is characterized by chronic, patchy, transmural inflammation of the entire gastrointestinal tract, while ulcerative colitis (UC) is manifested by chronic, continuous, superficial inflammation of the colon. Matrix metalloproteinases (MMPs) constitute a family of matrix degrading zinc and calcium-activated neutral endoproteinases, implicated in a wide range of biological processes. We found a marked upregulation of MMP-1, -2, -3 and -9 relative to their natural inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMP) -1 and/or -2, in inflamed mucosa of IBD patients, paralleled by an increase in net MMP activity. Administration of TNF-alpha neutralizing antibody infliximab® decreased MMP-1, -3 and -9 expression by cultured intestinal IBD explants and serum MMP-9 levels in CD patients, while MMP-2 levels remained almost the same. These observations suggest diverse regulator y pathways for the MMPs examined and a mechanistic pathway for infliximab® in the treatment of CD. The T allele at TIMP-1 SNP locus +372 T/C, downregulating TIMP-1, appeared to enhance CD susceptibility and worsen prognosis of these patients. Ultimately, these studies might give rationale for the development of novel therapeutic drugs in IBD, based on the inhibition or activation of one or more members of the matrix metalloproteinases family.
Description: Promotor: C.B.H.W. Lamers, Co-promotor: H.W. Verspaget
With summary in Dutch
Faculty: LUMC
Citation: Meijer, M. J.-W., 2009, Doctoral thesis, Leiden University
ISBN: 9789090240770
Handle: http://hdl.handle.net/1887/13749
 

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