Critical role of Keratin 1 in maintaining epithelial barrier and correlation of its down-regulation with the progression of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is the result of a chronic intestinal inflammatory response which usually occurred in colon and small intestine. Keratins constitute the intermediate filament cytoskeleton in all epithelia. The present study was intended to explore the role of Keratin 1 (KRT1) in the progress of IBD. In normal intestinal tissue, the expression of KRT1 was detected by RT-PCR and Western blot. The levels of KRT1 protein significantly decreased in serum samples of IBD patients as compared with sera of healthy controls. Immunohistochemistry revealed that the expression of KRT1 decreased in various intestinal diseases, especially in Crohn's disease and ulcerative colitis. Furthermore, down-regulated KRT1 was correlated with the severity of IBD. The overexpression of KRT1 maintained epithelial barrier in Caco-2 cells after IL-1β treatment. Furthermore, IL-1β-induced disruption of tight junction became significantly attenuated in KRT1 over-expressing Caco-2 cells as compared with control cells. Thus, KRT1 played an important role of maintaining epithelial barrier and its down-regulation in intestinal tissue was correlated with the progression of IBD.

Keywords: Cytoskeleton; Epithelial barrier; Inflammatory bowel disease; Keratin; Tight junction.