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New therapeutic targets in the treatment of ulcerative colitis

Social, environmental and dietary changes are associated with the changes of disease spectrum in a country. Ulcerative colitis has become a commonly seen disease in China, probably due to extensive consumption of Western foods in recent years. Unfortunately, the etiology and pathogenesis of ulcerative colitis have not been clarified yet. Therefore, no effective etiological treatment is available at present. But a recent study published in issue 44 of the World Journal of Gastroenterology may offer new insight into this difficult-to-treat disease.

A research team from the First Affiliated Hospital of Dalian Medical University's Department of Gastroenterology, China, led by Professor Ying-De Wang, investigated the expression of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor- (TNF-alpha). MMP-1 is a peptidase that degrades the extracellular matrix in the colonic mucosa, while TNF-alpha is an important and harmful inflammatory cytokine produced in macrophages in colon. The research team found that both MMP-1 and TNF-alpha were over expressed in the colonic mucosa of patients with ulcerative colitis. The over expressed MMP-1 excessively degrades the extracellular matrix, and subsequently damages the colonic mucosa and causes ulceration and inflammatory changes in ulcerative colitis, and the over expressed TNF-alpha directly damages the colon mucosa. MP-1 and TNF-alpha proteins have the so-called synergistic action. The study revealed that the excessively expressed TNF-alpha stimulated MMPs secreting cells to produce more MMP-1, aggravating the mucosa damage. Meanwhile, MMP-1 promoted secretion of TNF-alpha in a positive feedback manner to cause further injury in the mucosa of colon. So it is very likely both MMP-1 and TNF-alpha play a central role in the development of ulcerative colitis.

Because of the important functions of MMP-1 and TNF-alpha in the development of ulcerative colitis, they have become therapeutic targeting proteins in the treatment of ulcerative colitis. It has been reported that agents of MMPs inhibitor and anti-TNF-alpha antibody were developed in Europe and America. For example, a TNF-alpha antagonist, Infliximab, has been shown to be effective against adult and child patients with ulcerative colitis. It has been approved by the FDA for clinical use in patients with Crohn's disease, another inflammatory bowel disease similar to ulcerative colitis. But MMPs inhibitor has only been used to treat experimental animal models of ulcerative colitis. The clinical application of MMPs inhibitor awaits future studies.

The results of this study will undoubtedly bring about a new round of research on the pathogenesis and new methods of treating ulcerative colitis. This will be a step toward a promising future in the battle against ulcerative colitis.


Contact: You-De Chang
World Journal of Gastroenterology

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