MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease

被引：54

作者：

Banerjee, S. ^{[1
]}

Oneda, B. ^{[2
]}

Yap, L. M. ^{[3
]}

Jewell, D. P. ^{[4
]}

Matters, G. L. ^{[1
]}

Fitzpatrick, L. R. ^{[5
]}

Seibold, F. ^{[6
]}

Sterchi, E. E. ^{[2
]}

Ahmad, T. ^{[7
]}

Lottaz, D. ^{[2
,8
]}

Bond, J. S. ^{[1
]}

机构：

[1] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA

[2] Univ Bern, Inst Biochem & Mol Med, Bern, Switzerland

[3] Alfred, Dept Gastroenterol, Melbourne, Vic, Australia

[4] Univ Oxford, Radcliffe Infirm, Gastroenterol Unit, Oxford OX2 6HE, England

[5] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA USA

[6] Univ Bern, Dept Gastroenterol, Bern, Switzerland

[7] Royal Devon & Exeter Hosp, Dept Gastroenterol, Exeter EX2 5DW, Devon, England

[8] Univ Bern, Inselspital, Dept Rheumatol Clin Immunol & Allergol, CH-3010 Bern, Switzerland

来源：

MUCOSAL IMMUNOLOGY | 2009年 / 2卷 / 03期

基金：

英国惠康基金;

关键词：

DEXTRAN SULFATE SODIUM; INTESTINAL EPITHELIAL-CELLS; GENOME-WIDE ASSOCIATION; INBRED MOUSE STRAINS; ULCERATIVE-COLITIS; CROHNS-DISEASE; BETA-SUBUNITS; METALLOENDOPEPTIDASE MEPRIN; MATRIX METALLOPROTEINASES; DIFFERENTIAL EXPRESSION;

D O I：

10.1038/mi.2009.3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The MEP1A gene, located on human chromosome 6p (mouse chromosome 17) in a susceptibility region for inflammatory bowel disease (IBD), encodes the alpha-subunit of metalloproteinase meprin A, which is expressed in the intestinal epithelium. This study shows a genetic association of MEP1A with IBD in a cohort of ulcerative colitis (UC) patients. There were four single-nucleotide polymorphisms in the coding region (P = 0.0012-0.04), and one in the 3 '-untranslated region (P = 2 x 10(-7)) that displayed associations with UC. Moreover, meprin-alpha mRNA was decreased in inflamed mucosa of IBD patients. Meprin-alpha knockout mice exhibited a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium. Collectively, the data implicate MEP1A as a UC susceptibility gene and indicate that decreased meprin-alpha expression is associated with intestinal inflammation in IBD patients and in a mouse experimental model of IBD.

引用

页码：220 / 231

页数：12

共 48 条

[1] Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer [J].

Atreya, R ;

Neurath, MF .

CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 2005, 28 (03) :187-195

[2] Prointerleukin-18 Is Activated by Meprin β in Vitro and in Vivo in Intestinal Inflammation [J].

Banerjee, Sanjita ;

Bond, Judith S. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (46) :31371-31377

[3] Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease [J].

Banks, C ;

Bateman, A ;

Payne, R ;

Johnson, P ;

Sheron, N .

JOURNAL OF PATHOLOGY, 2003, 199 (01) :28-35

[4] Expression and distribution of meprin protease subunits in mouse intestine [J].

Bankus, JM ;

Bond, JS .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1996, 331 (01) :87-94

[5] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[6] Probing the active sites and mechanisms of rat metalloproteases meprin A and B [J].

Bertenshaw, GP ;

Villa, JP ;

Hengst, JA ;

Bond, JS .

BIOLOGICAL CHEMISTRY, 2002, 383 (7-8) :1175-1183

[7] Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity [J].

Bertenshaw, GP ;

Turk, BE ;

Hubbard, SJ ;

Matters, GL ;

Bylander, JE ;

Crisman, JM ;

Cantley, LC ;

Bond, JS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (16) :13248-13255

[8] DEFICIENCY OF A KIDNEY METALLOPROTEINASE ACTIVITY IN INBRED MOUSE STRAINS [J].

BEYNON, RJ ;

BOND, JS .

SCIENCE, 1983, 219 (4590) :1351-1353

[9] Insights from mouse models of colitis [J].

Boismenu, R ;

Chen, YP .

JOURNAL OF LEUKOCYTE BIOLOGY, 2000, 67 (03) :267-278

[10] Meprin metalloprotease expression and regulation in kidney, intestine, urinary tract infections and cancer [J].

Bond, JS ;

Matters, GL ;

Banerjee, S ;

Dusheck, RE .

FEBS LETTERS, 2005, 579 (15) :3317-3322

← 1 2 3 4 5 →