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

Felicitas L. Koller, E. Ashley Dozier, Ki Taek Nam, Mei Swee, Timothy P. Birkland, William C. Parks, Barbara Fingleton

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) represent serious health burdens because of both the tissue-damaging disease itself and 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 sulfate 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.

Original languageEnglish
Pages (from-to)1749-1759
Number of pages11
JournalLaboratory Investigation
Volume92
Issue number12
DOIs
Publication statusPublished - 2012 Dec 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia'. Together they form a unique fingerprint.

  • Cite this