Malin Johansson research group
Our gastrointestinal tract is exposed to our environment by everything that we ingest. In addition the epithelium is exposed to other hazards as hydrochloric acid, high bicarbonate, digestive enzymes, bile acid and large amounts of bacteria. The bacterial load increases distally and is an extreme challenge in colon with more than 1 kg of bacteria in an adult human. The outermost defense of the gastrointestinal tract is secreted mucus. In colon it forms a physical barrier of densely packed and well-organized mucus with the MUC2 mucin as the core network. This creates a zone restricting bacteria from contact with the epithelium. The turnover of the inner mucus layer is very rapid (1-2 h), as analyzed by in vivo labeling of mucin O-glycans, to maintain its protective function. Mice devoid of mucus show massive bacterial contact, develop colitis and later colon cancer. We assess the mucus thickness and quality as a barrier on live explants from mouse colon explants or human colonic biopsies and have found defects in the inner mucus layer both in colitis models and ulcerative colitis (UC) patients. The molecular details causing these defects are not known today and our work is along the model that the inner mucus layer is the key to understand the mechanisms behind UC. IL10-/- mice have a malfunctioning inner mucus layer and are used as a model to elucidate the problem where ion transport, mucus composition, and turnover are key factors. We are testing interventions to correct the defects that can be potential treatment targets. We are setting up methods to study mucus secretion from goblet by confocal microscopy on live explants and the maturation of different goblet cell types is investigated in Spdef-/- mice, a transcription factor involved in terminal differentiation. CLCA1, a mucus protein with unknown function is studied to identify its contribution to the formation of protective mucus. A better molecular understanding of defects in protection of the epithelium and defects causing disease is important to develop better treatment strategies for UC patients.
More info: http://www.medkem.gu.se/mucinbiology/