Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease

Vizoso, F; Corte, M.D.; Bongera, Miguel; Martínez, Aránzazu; Martin, Adam P.; Andicoechea, Alejandro; Gava, Rodrigo

doi:10.1080/00365520600554667

Cited by 24 publications

(22 citation statements)

References 24 publications

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“…A group studying the Na + /H + exchanger (NHE3) discovered that NHE3 −/− mice developed spontaneous colitis restricted to the mucosa of the distal colon with a concomitant 15-fold increase in MMP-8 expression [ 42 ]. MMP-13 has also shown to be present in the inflamed areas of colon in IBD patients but absent in noninflamed colons or in acute diverticulitis and MMP-13 expression correlated with histological measures of disease [ 43 ].…”

Section: Association Between Mmps and Ibd: Enzymes Involved And Cementioning

confidence: 99%

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

O'Sullivan

Gilmer

Medina

2015

Mediators of Inflammation

133

119

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Matrix metalloproteinases (MMPs) are known to be upregulated in inflammatory bowel disease (IBD) and other inflammatory conditions, but while their involvement is clear, their role in many settings has yet to be determined. Studies of the involvement of MMPs in IBD since 2006 have revealed an array of immune and stromal cells which release the proteases in response to inflammatory cytokines and growth factors. Through digestion of the extracellular matrix and cleavage of bioactive proteins, a huge diversity of roles have been revealed for the MMPs in IBD, where they have been shown to regulate epithelial barrier function, immune response, angiogenesis, fibrosis, and wound healing. For this reason, MMPs have been recognised as potential biomarkers for disease activity in IBD and inhibition remains a huge area of interest. This review describes new roles of MMPs in the pathophysiology of IBD and suggests future directions for the development of treatment strategies in this condition.

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Section: Association Between Mmps and Ibd: Enzymes Involved And Cementioning

confidence: 99%

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

O'Sullivan

Gilmer

Medina

2015

Mediators of Inflammation

133

119

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“…In colonic tissue from CD patients, MMP-13 staining was observed in only a few tissues and no differences could be observed between CD and control tissue (Stumpf et al, 2005). The expression of MMP-13 was further investigated by Vizoso et al in mucosal biopsies from UC and CD patients (Vizoso et al, 2006). More than 60% of patients with UC and 50% of patients with CD had MMP-13 expression in inflamed tissue.…”

Section: Mmp-13mentioning

confidence: 99%

The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases

Bruyn¹,

Vandooren

Ugarte-Berzal

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels.

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“…Significantly increased levels of MMP13 mRNA were found in IBD biopsy specimens (Rath et al, ). Moreover, a positive correlation was found between MMP13 expression and the histological inflammation scores in mucosal samples from IBD patients (Vizoso et al, ). Recently, both endothelial cells and infiltrating leucocytes were identified as the major sources of MMP13 in UC (Rath et al, ).…”

Section: Introductionmentioning

confidence: 97%

Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

Vandenbroucke¹,

Dejonckheere²,

Hauwermeiren³

et al. 2013

EMBO Mol Med

118

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Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13−/− mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13−/− mice compared to MMP13+/+ mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13−/− mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential.

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Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease

Cited by 24 publications

References 24 publications

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases

Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

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