A variant form of the human deleted in malignant brain tumor 1 (DMBT1) gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3)

PLoS One. 2013 May 15;8(5):e64441. doi: 10.1371/journal.pone.0064441. Print 2013.


The protein deleted in malignant brain tumors (DMBT1) and the trefoil factor (TFF) proteins have all been proposed to have roles in epithelial cell growth and cell differentiation and shown to be up regulated in inflammatory bowel diseases. A panel of monoclonal antibodies was raised against human DMBT1(gp340). Analysis of lung washings and colon tissue extracts by Western blotting in the unreduced state, two antibodies (Hyb213-1 and Hyb213-6) reacted with a double band of 290 kDa in lung lavage. Hyb213-6, in addition, reacted against a double band of 270 kDa in colon extract while Hyb213-1 showed no reaction. Hyb213-6 showed strong cytoplasmic staining in epithelial cells of both the small and large intestine whereas no staining was seen with Hyb213-1. The number of DMBT1(gp340) positive epithelial cells, stained with Hyb213-6, was significantly up regulated in inflammatory colon tissue sections from patients with ulcerative colitis (p<0.0001) and Crohn's disease (p = 0.006) compared to normal colon tissue. Immunohistochemical analysis of trefoil factor TFF1, 2 and 3 showed that TFF1 and 3 localized to goblet cells in both normal colon tissue and in tissue from patients with ulcerative colitis or Crohn's disease. No staining for TFF2 was seen in goblet cells in normal colon tissue whereas the majority of tissue sections in ulcerative colitis and Crohn's disease showed sparse and scattered TFF2 positive goblet cells. DMBT1 and TFF proteins did therefore not co-localize in the same cells but localized in adjacent cells in the colon. The interaction between DMBT1(gp340) and trefoil TFFs proteins was investigated using an ELISA assay. DMBT1(gp340) bound to solid-phase bound recombinant dimeric TFF3 in a calcium dependent manner (p<0.0001) but did not bind to recombinant forms of monomeric TFF3, TFF2 or glycosylated TFF2. This implies a role for DMBT1 and TFF3 together in inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Peptides / genetics*
  • Peptides / metabolism
  • Protein Binding
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Tumor Suppressor Proteins
  • Up-Regulation


  • Calcium-Binding Proteins
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Peptides
  • Receptors, Cell Surface
  • Recombinant Proteins
  • TFF2 protein, human
  • TFF3 protein, human
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Tumor Suppressor Proteins

Grant support

Indian Statistical Institute, Indian Statistical Institute, Kolkata, India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.