Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease

Lampe, B; Barthel, Brandon; Coupland, Sarah E.; Riecken, Ernst–Otto; Rosewicz, Stefan

doi:10.1136/gut.47.1.63

Cited by 341 publications

(255 citation statements)

References 45 publications

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“…Cornelius et al (36) have indicated dual roles for MMPs in angiogenesis acting as proangiogenic mediators during tissue remodeling and then as antiangiogenic mediators through generation of angiostatin preventing vessel maturation. Additionally, overexpression of MMPs and TIMPS during UC has been shown by von Lampe et al (163). Thus MMPs function in IBD angiogenesis may contribute to the pathology of disease by inhibition of vascular maturation while promoting early vessel growth.…”

Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 84%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

144

114

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Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

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Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 84%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

144

114

View full text Add to dashboard Cite

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“…Also, there is some hope that multiple subtypes of cancers may converge upon up-regulating a relatively limited repertoire of proteases, giving each successful substrate a wider range of clinical indications. (viii) Proteases that are or can become extracellular are crucial to many other disease processes, including thrombosis, congestive heart failure, inflammation, neurodegeneration, and infectious pathogens (34)(35)(36)(37). We are not even limited to proteases: Any conditions that sever the vetoing polyanion from the polycation (e.g., agents that reduce disulfide bonds) offer potential mechanisms for localization.…”

Section: Discussionmentioning

confidence: 99%

Tumor imaging by means of proteolytic activation of cell-penetrating peptides

Jiang

Olson

Nguyen

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

766

713

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We have devised and tested a new strategy for selectively delivering molecules to tumor cells. Cellular association of polyargininebased, cell-penetrating peptides (CPPs) is effectively blocked when they are fused to an inhibitory domain made up of negatively charged residues. We call these fusions activatable CPPs (ACPPs) because cleavage of the linker between the polycationic and polyanionic domains, typically by a protease, releases the CPP portion and its attached cargo to bind to and enter cells. Association with cultured cells typically increases 10-fold or more upon linker cleavage. In mice xenografted with human tumor cells secreting matrix metalloproteinases 2 and 9, ACPPs bearing a far-red-fluorescent cargo show in vivo contrast ratios of 2-3 and a 3.1-fold increase in standard uptake value for tumors relative to contralateral normal tissue or control peptides with scrambled linkers. Ex vivo slices of freshly resected human squamous cell carcinomas give similar or better contrast ratios. Because CPPs are known to import a wide variety of nonoptical contrast and therapeutic agents, ACPPs offer a general strategy toward imaging and treating disease processes associated with linker-cleaving activities such as extracellular proteases.cancer ͉ molecular imaging ͉ polycation ͉ transduction

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“…In this respect it was recently shown that spontaneous and TNF-α-induced single-cell apoptosis results in leaks in the epithelial barrier (Gitter et al, 2000). Moreover, it was demonstrated that metalloproteinase levels are elevated in inflammatory bowel diseases (Baugh et al, 1999;von Lampe et al, 2000). Downregulation of occludin thus appears to be at least one of the molecular events participating in the increase of paracellular permeability (Kucharzik et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

The specific fates of tight junction proteins in apoptotic epithelial cells

Bojarski

Weiske

Schöneberg³

et al. 2004

Journal of Cell Science

159

129

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The polarized morphology of epithelial cells depends on the establishment and maintenance of characteristic intercellular junctions. The dramatic morphological changes observed in apoptotic epithelial cells were ascribed at least in part to the specific fragmentation of components of adherens junctions and desmosomes. Little, however, is known about tight junctions during apoptosis. We have found that after induction of apoptosis in epithelial cells, tight junction proteins undergo proteolytic cleavage in a distinctive manner correlated with a disruption of tight junctions. The transmembrane protein occludin and, likewise, the cytoplasmic adaptor proteins ZO-1 and ZO-2 are fragmented by caspase cleavage. In addition, occludin is cleaved at an extracellular site by a metalloproteinase. The caspase cleavage site in occludin was mapped C-terminally to Asp320 within the C-terminal cytoplasmic domain. Mutagenesis of this site efficiently blocked fragmentation. In the presence of caspase and/or metalloproteinase inhibitors, fragmentation of occludin, ZO-1 and ZO-2 was blocked and cellular morphology was almost fully preserved. Interestingly, two members of the claudin family of transmembrane tight junction proteins exhibited a different behavior. While the amount of claudin-2 protein was reduced similarly to occludin, ZO-1 and ZO-2, claudin-1 was either fully preserved or was even increased in apoptotic cells.

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Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease

Cited by 341 publications

References 45 publications

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Tumor imaging by means of proteolytic activation of cell-penetrating peptides

The specific fates of tight junction proteins in apoptotic epithelial cells

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