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Overexpression of abnormal epithelial glycoprotein MUC1 is associated with pancreatitis and other extraintestinal complications in inflammatory bowel disease (IBD)
Author(s) -
Beatty Pamela,
Kadayakkara Deepak,
Turner Michael,
Janjic Jelena,
Ahrens Eric,
Finn Olivera
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.450
Subject(s) - inflammatory bowel disease , medicine , colorectal cancer , pancreatitis , pancreatic cancer , immunohistochemistry , muc1 , inflammation , pancreas , genetically modified mouse , cancer , pathology , disease , gastroenterology , cancer research , immunology , transgene , biology , biochemistry , gene
IBD patients are at increased risk for colon cancer and extraintestinal complications including pancreatitis, the mechanisms of which are poorly understood. Earlier studies have shown that overexpression of hypoglycosylated (abnormal) form of epithelial MUC1 in colon accelerates the progression of IBD and colon cancer. Our data suggest that abnormal MUC1 expression is also responsible for the extraintestinal manifestations of IBD. We generated TCR transgenic mice specific for hypoglycosylated MUC1. We transferred T cells labeled with perfluoropolyether (PFPE) nanoemulsions into MUC1 transgenic mice with IBD. Three days later, we quantified the biodistribution of transferred cells in various organs by 19 F NMR spectroscopy. The transferred T cells migrated as expected to the colon only in mice with disease. Unexpectedly, large numbers of T cells migrated to pancreas and liver. Immunohistochemistry showed increased expression of abnormal MUC1 in pancreatic acini and ducts in mice with IBD. This change appears sufficient to drive high levels of inflammation causing pancreatitis and liver problems. Thus, we conclude that abnormal expression of MUC1 plays an important role in the intestinal and extraintestinal manifestations of IBD in these animals. This work is supported by Cancer Research and Prevention Foundation (P.L.B), RO1 56103 (O.J.F.) and NIH R01‐EB003453 and P41‐EB001977 (E.T.A).