The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

Lakatos, Gábor; Hritz, István; Varga, Mária Zsófia; Juhász, Márk; Miheller, Pál; Cierny, Gabriel; Tulassay, Zsolt; Herszényi, László

doi:10.1159/000336995

Cited by 79 publications

(65 citation statements)

References 122 publications

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“…We confirm the previous observations made by Lakatos et al 4 in their study which demonstrated that serum antigen concentrations TIMP-1 were significantly increased in patients with UC and CD compared to controls. These data are in agreement with our study in which TIMP-1 antigen levels were highest in the IBD group (p<0.006).…”

Section: Discussionsupporting

confidence: 93%

“…These proteins have been shown to be associated with disease activity as well as extraintestinal finding development. 4 The function of MMPs, a family of Zn 2+ -dependent endopeptidases, in the degradation of extracellular matrix components during tumor invasion and metastasis as well as their role in the processes of tissue destruction and remodeling during inflammation have been proposed. [5][6][7] The natural inhibitors of MMPs are called tissue inhibitors of metalloproteinases (TIMPs).…”

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confidence: 99%

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Association of Matrix Metalloproteinases and Their Tissue Inhibitor With Disease Activity and Development in Spondyloarthropathy and Inflammatory Bowel Disease

et al. 2015

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Extra-intestinal involvement is a common manifestation in Inflammatory Bowel Disease (IBD). Joints are the most common site of involvement and the co-existence of IBD with spondylitis or peripheral arthritis (Asymmetric arthritis on lower extremity joints) is considered as Spondiloarthropathy (SpA), "enteropathic arthritis" or "arthritis related to IBD" according to the "European Spondiloartropathy Study Group" criteria.1,2 The pathogenesis of extra-intestinal findings in IBD is poorly understood. Current theories suggest the impairment of mucosal immunoregulatory mechanisms in IBD, resulting in the transport of luminal content antigens to the systemic circulation. Also, lack of intestinal mucosal barrier protection mechanism, mucosal secretion of immunoglobulin A (IgA) and defense mechanism of mucosa against foreign proteins ABSTRACT Objectives: This study aims to investigate whether clinical measures of disease activity and function in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are associated with matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase -1 (TIMP-1), and if MMPs can be more useful than C-reactive protein and erythrocyte sedimentation rate in predicting disease activity in AS. Patients and methods: MMP-3, MMP-9 and TIMP-1 levels were measured by ELISA in 20 patients with AS, 20 patients with IBD, 20 patients with IBD and AS (35 males, 25 females; mean age 38.1 years; range 19 to 62 years), and 20 healthy volunteers (10 males, 10 females; median age 38.5 years; range 24 to 63 years) as a control group. Bath Ankylosing Spondylitis Disease Activity Index, Truelove-Witts activity criteria for ulcerative colitis, and Crohn's Disease of Activity Index scoring systems were used. Results: Highest MMP-3 level was in IBD group (33.51±59.56 ng/mL, p<0.045). MMP-3 levels were significantly higher in patients with IBD and IBD+AS than in patients with AS (p<0.007 and p<0.035, respectively). Highest MMP-9 levels were in the control group (10.35±2.61 ng/mL, p<0.48). MMP-9 levels were higher in AS group patients than those in IBD and IBD+AS groups, but the difference was not statistically significant (p<0.494 and p<0.260, respectively). Highest TIMP-1 levels were in the IBD group (8.11 ng/mL, p<0.006). TIMP-1 levels of IBD group were significantly higher than both AS and IBD+AS groups (p<0.033 and p<0.008, respectively). A statistically significant correlation was detected between serum MMP-3 levels and disease activity and Bath Ankylosing Spondylitis Disease Activity Index score in patients with AS (r=0.841, p<0.05). Conclusion: We concluded that serum MMP-3 levels may be a better biomarker than C-reactive protein and erythrocyte sedimentation rate in showing disease activity in AS.Keywords: Ankylosing spondylitis; inflammatory bowel disease; metalloproteinase-3; metalloproteinase-9; tissue matrix metalloproteinase inhibitor-1.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Association of Matrix Metalloproteinases and Their Tissue Inhibitor With Disease Activity and Development in Spondyloarthropathy and Inflammatory Bowel Disease

et al. 2015

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“…Population-based studies have found that approximately 20% of patients developed fibrotic stricture within 20 years of a CD diagnosis; > 30% develop this complication within 10 years of diagnosis at tertiary referral centers. About 50% CD patients will develop penetrating or fibrotic strictures, and 70% of them will need surgery eventually [6][7][8]. Surgery is the only choice for symptoms/ complex stenosis.…”

Section: Introductionmentioning

confidence: 99%

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

et al. 2019

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Background: Intestinal fibrosis is the major complication of Crohn’s disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. Methods: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-β1 (TGF-β1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-β/Smad pathway. Results: The results showed that the concentration of CA was 12.5, 25, 50 μmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-β/Smad signaling pathway. Conclusion: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-β/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-β1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-β/Smad pathway.

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“…The tissue damage in IBD is mediated by an overactive mucosal immune response arising from a complex interplay of genetic, environmental and immunological factors. In the pathophysiological process of IBD, a variety of inflammatory mediators such as proteolytic enzymes, cytokines, reactive oxidative species, and growth factors are implicated in the complex tissue injury processes [1,2,3,4]. The link between IBD and colorectal cancer (CRC) has been described nearly a century ago [5].…”

Section: Introductionmentioning

confidence: 99%

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Herszényi¹,

Barabás

Miheller³

et al. 2014

Dig Dis

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Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.

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The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

Cited by 79 publications

References 122 publications

Association of Matrix Metalloproteinases and Their Tissue Inhibitor With Disease Activity and Development in Spondyloarthropathy and Inflammatory Bowel Disease

Association of Matrix Metalloproteinases and Their Tissue Inhibitor With Disease Activity and Development in Spondyloarthropathy and Inflammatory Bowel Disease

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

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