Tissue regeneration mechanism in inflammatory bowel disease
The intestinal lumen is lined with a single layered epithelium that protects the body from contents of the lumen such as pathogens. As integrity of the epithelium is essential for good health, complete healing of the lining is crucial and can be made possible by anti-inflammatory drugs. Unfortunately, on top of sometimes unpleasant side-effects, groups of patients do not respond to this standard therapy. As little is known about the process of regeneration after excessive injury or inflammation, the EU-funded EPIREP project investigated the dynamics of the changes taking place. The researchers focused on the transitional cellular fate of the intestinal epithelial cells during regeneration. EPIREP used the dextran sulfate sodium (DSS) colitis model, which is widely accepted as a model of human colitis in rodents. Presenting ideal materials to analyse the process, the whole process can be characterised from a cellular, transcriptional and signalling perspective. Unique surface antigens that appear during regeneration in the repairing epithelium (RE) were isolated. Comprehensive gene expression analysis revealed that the RE has a distinct transcriptional profile when compared to the homeostatic epithelium. Interestingly, the adaptive response revealed reprogramming into a more primitive state and identified a family of transcriptional regulators as the main driver of this process. Analysis of the upstream activators of the pathway showed strong evidence of activation of the entire signalling pathway uniquely to the RE. Based on these in vivo observations, the project researcher recreated the cellular environment in vitro and demonstrated that the observed pathway is required for reprogramming cells into the more primitive state. Moreover, results indicated that this adaptive response leading to the formation of the RE is completely transitional and fully reversible. The EPIREP project has built a model of the process that defines components that act synergistically to create the primitive transitional state necessary for tissue regeneration. Results may be applicable to other regenerative processes in epithelial tissues such as cardiovascular and respiratory tracts.
Keywords
Tissue regeneration, inflammatory bowel disease, epithelium, EPIREP, transitional