Function and regulation of the multidrug resistance-associated protein 1 during inflammatory bowel disease and liver regeneration

PhD ceremony: Mr. A. van Steenpaal, 13.15 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Function and regulation of the multidrug resistance-associated protein 1 during inflammatory bowel disease and liver regeneration

Promotor(s): prof. K.N. Faber, prof. A.J. Moshage

Faculty: Medical Sciences

The transport protein MRP1 has an important function in controlling the activity and/or viability of various cell types in the intestine and liver during inflammation. Its effects can be more or less favourable in different cell types.

The Multidrug Resistance-associated Protein 1 (MRP1) is s major subject of scientific and clinical research due to its key role in multidrug resistance. MRP 1 also serves important physiological functions by transporting endogenous inflammatory compounds.

MRP1 levels are increased in inflamed intestinal tissues of patients with Crohn’s disease and ulcerative colitis, specifically in regions containing intestinal stem cells, and in cells of the adaptive immune system, the T-lymphocytes. Research revealed that MRP1 protects intestinal stem cells against inflammation-induced cell death, whereas MRP1 expression increases the sensitivity of T-lymphocytes to inflammation-induced cell death. In an animal model, the presence of MRP1 was found to be required for optimal stem cell activation during severe liver disease. However, it’s absence did not lead to significant delay of liver regeneration.