Increased expression of Deleted in Malignant Brain Tumors (DMBT1) gene in advanced precancerous gastric lesions in three ethnic populations: effect of modulation on mouse mucous metaplasia in response to H. pylori infection

Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Recent studies have shown that DMBT1 expression is up-regulated in areas of intestinal metaplasia and in gastric tumors. Here, we examined the role of DMBT1 in the development of inflammatory response and gastric precancerous lesions in Caucasian, African American and Hispanic populations as well as in a mouse model. We found that mucosal DMBT1 expression is significantly increased in individuals with more advanced gastric precancerous lesions. We also show that H. pylori infection of Dmbt1-/- mice results in enhanced gastric inflammation and the development of mucous metaplasia that is accompanied by increased cell proliferative rates and reduced IL-33 expression levels in the inflamed mucosa. Taken together, our data suggest that DMBT1 may be mediating mucosal protection that may reduce the risk of developing gastric precancerous lesions in response to H. pylori infection Microarray from gastric tissues of Hispanic individuals with different stages of gastritis (MAG, IM and dysplasia) were analyzed to determine gene sets associated with stage of gastritis. The study was validated by real-time PCR in 3 different ethnic groups (African Americans, Caucasian and Hispanic) and the role of the identified gene was determined in mouse models (C57Bl/6) of H. pylori infection. Please note that the RT-PCR data is not included in the records.