Matrix metalloproteinases (MMPs) are responsible for the turnover and degradation of extracellular matrix. They play a crucial role in the growth and migration of colorectal carcinoma cells. Colorectal carcinomas are characterized by enhanced expression of MMP-2, MMP-9, MMP-7, and MMP-13. The aim of this study was to determine the expression levels of MMP-2, MMP-9, MMP-7, MMP-13, and MMP-14 and their specific inhibitor TIMP-1 in inflammatory bowel diseases and precancerous lesions of the colon, i.e., Crohn's disease and ulcerative colitis, and in adenomatous polyps (APs) for comparison. Biopsy samples of pathological and healthy tissue were obtained from 40 patients with inflammatory bowel disease (ulcerative colitis, n = 17; Crohn's disease, n = 23) and from 19 patients with APs. mRNA was measured by quantitative real-time polymerase chain reaction to study MMP and TIMP-1 gene expression in both pathological and normal mucosal specimens. For MMP-2, MMP-9, and TIMP-1, protein expression also was quantified with sandwich enzyme-linked immunosorbent assay. In biopsy specimens of Crohn's disease and ulcerative colitis, significantly increased levels of MMP-2, MMP-7, and MMP-13 mRNA were found. MMP-2 and MMP-9 showed enhanced secretion on the protein level. AP revealed an increased transcription of MMP-7 and MMP-13 genes. MMP-14 mRNA was decreased in APs. MMPs, especially MMP-7 and MMP-13, which are expressed primarily on the tumor cell surface, are elevated in inflammatory bowel disease, which may have more chance to evolve into malignancy than normal tissue. In APs, increased expression of MMP-7 and MMP-13 may serve as an early indicator for colorectal carcinogenesis.
Matrix Metalloproteinases (MMPs) are a family of Zn (2 +)-dependent endopeptidases that are considered to be the most potent proteases in the turnover of the extracellular matrix (ECM). In addition to their capability for degradating virtually all protein components of the ECM, MMPs regulate a variety of non-matrix substrates such as chemokines, cytokines and growth factors. Therefore MMPs play a central role in a variety of physiological and pathological processes such as angiogenesis, wound healing and inflammatory response including mucosal inflammation associated with inflammatory bowel disease (IBD). Apart from mucosal destruction in IBD, recent studies have identified several new functions of MMPs for the pathophysiology of the healthy and inflamed intestine. This article summarises the main activities of MMPs in IBD with emphasis on their pathophysiological relevance and potential clinical implications based on the expression and regulation patterns of these enzymes.
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