Abstract
Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), are produced in the gastrointestinal tract by several structural cells. The balance between MMPs and TIMPs is essential for many physiological processes in the gut. However, imbalance between MMPs and TIMPs plays an important role in the pathophysiology of diverse intestinal inflammatory conditions. We reviewed the role of the MMP/TIMP system in the pathogenesis of intestinal inflammatory diseases and pharmacologic perspectives for the use of compounds that restore the MMP/TIMP balance.
Footnotes
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This work was supported in part by a grant from the Secretaria de Estado de Educacion y Universidades fellowship, cofunded by the European Social Fund (to C.M.), and by Instituto de Salud Carlos III (C03/02) (Madrid, Spain). C.M. is a postdoctoral fellow of Spanish Ministry of Education.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.103465.
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ABBREVIATIONS: MMP, matrix metalloproteinases; TIMP, endogenous inhibitor of matrix metalloproteinases; ECM, extracellular matrix; IBD, inflammatory bowel disease; TNBS, trinitrobenzene sulfonic acid; CD, Crohn's disease; IL, interleukin; UC, ulcerative colitis; TNF-α, tumor necrosis factor-α; DSS, dextran sulfate sodium; CT1399, N4-hydroxy-N′-[1-(S)-morpholiosulfonylaminoethyl aminocarbonyl-2-cyclohexylethyl]-2-(R)-(4-chlorophenylpropyl) succinamide; CGS-27023-A, [N-hydroxyl-2(R)-(4-methoxysulfonyl) 3-piconyl)-(amino-3 methylbutaneamide hydrochloride monohydrate)]; ONO-4817, (2S,4S)-N-hydroxy-5-ethoxy-methyloxy-2-methyl-4-(4-phenoxylbenzoyl) aminopentanamide.
- Received March 1, 2006.
- Accepted April 24, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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