Rol de las uniones estrechas del epitelio intestinal en la patogenia de la enfermedad de Crohn

Abstract

Crohn’s disease is an inflammatory bowel disease that affects the intestinal wall. This wall consists of an epithelial cell layer that forms a continuous polarized monolayer, closely connected by various types of cellular junctions. Among these, tight junctions play a relevant role. They form a continuous structure delimiting the apical and basolateral domains in epithelial and endothelial cells, creating in this way a selective paracellular barrier, fundamental for the homeostasis of the organism. There is increasing evidence that the dysfunction of the epithelial barrier plays a central role in the physiopathology of Crohn’s disease. Crohn’s disease patients exhibit a loss of the barrier function of the tight junctions, an increased production of pro-inflammatory cytokines and dysregulation of the immune system. In his review the molecular composition, structure, interactions and function of the tight junctions are briefly described, and recent evidence on the relationship between the dysfunction of the tight junctions and Crohn’s disease is commented. The role of microbiota in the regulation of tight junctions and the participation of tight junctions deregulation in the development of cancer associated to Crohn’s disease are also detailed. Finally, recent findings about the employment of tight junctions as targets for the development of new drugs are described.

Keywords

• enfermedad de Crohn
• uniones estrechas
• claudina
• ocludina
• microbiota
• epitelio intestinal