Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

Biologic modelling of periodontal disease progression

“…Serum MMP‐1 and MMP‐9 have been associated with other chronic mucosal inflammatory processes, degradation of extracellular matrix and cleavage of substrates including growth factors and various cytokines and chemokines that play a role in many physiologic and pathophysiologic processes. MMPs have been reported to be elevated in the serum and local tissues of patients with various chronic inflammatory diseases including arthritis (Silosi et al., ), inflammatory bowel disease (Jakubowska et al., ) and vascular atherosclerosis (Abdelnaseer et al., ). In several cross‐sectional studies, levels of MMPs (e.g.…”

Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

“…It is well-established that matrix metalloproteinases (MMPs) are major contributors to the breakdown of extracellular matrix components in a variety of physiologic and pathologic processes, including colitis (Naito and Yoshikawa, 2005). Although the activity of MMPs is tightly controlled by TIMPs, whose level also increases in the course of inflammation, it is proposed that the overly increased elevation of MMPs and the consequent imbalance between MMPs and TIMPs play a crucial role in tissue injury (von Lampe et al, 2000;Jakubowska et al, 2016). Thus, it is conceivable that the strong elevation of TIMP-1 induced by BRL 44408 tips the imbalance in favor of TIMPs, which results in reduced tissue damage and improved healing processes.…”

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

“…In IBD patients, reports have demonstrated an increased level of several MMPs in inflamed intestine, which is often accompanied by an insufficient level of the endogenous MMP inhibitors such as tissue inhibitor of metalloproteinases (TIMPs) [103,104,105]. The activity of some MMPs (MMP-1, 2, 3 and 9) is also augmented in colon of IBD patients and is correlated with MPO level and tissue damage [106].…”