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Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia

Authors
 Felicitas L. Koller ; E. Ashley Dozier ; Barbara Fingleton ; William C. Parks ; Timothy P. Birkland ; Mei Swee ; Ki Taek Nam 
Citation
 Laboratory Investigation, Vol.92(12) : 1749~1759, 2012 
Journal Title
 Laboratory Investigation 
ISSN
 0023-6837 
Issue Date
2012
Abstract
Inflammatory bowel diseases such as ulcerative colitis represent serious health burdens, both because of the tissue-damaging disease itself, and because of an elevated risk of colon cancer. The increased expression of many members of the matrix metalloproteinase (MMP) family of enzymes that occurs in colitis, has long been associated with the destructive nature of the disease. Recent findings in cancer and other MMP-associated diseases, however, led us to question whether MMPs are indeed detrimental in the setting of colitis. Here, we focus on a single MMP family member, MMP10, and assess its role in a murine model of colonic tissue damage induced by dextran sulphate sodium (DSS) treatment. Using mice genetically deficient for MMP10, we find that absence of this enzyme leads to significantly worse disease scores and failure to resolve inflammation even after extended recovery periods. We show that MMP10 is produced predominantly by infiltrating myeloid cells in both murine and human colitis. Through bone marrow transplant experiments, we confirm that bone marrow-derived MMP10 contributes to colitis severity. Mice lacking MMP10 have a significantly higher propensity for development of dysplastic lesions in the colon after two rounds of DSS exposure. Thus, we conclude that MMP10 is required for resolution of DSS-induced colonic damage, and in its absence, chronic inflammation and ultimately dysplasia occurs.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/91374
DOI
10.1038/labinvest.2012.141
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
Yonsei Authors
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