The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction.

The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction. Am J Physiol Gastrointest Liver Physiol. 2016 Aug 4;:ajpgi.00441.2015 Authors: Ronaghan NJ, Shang J, Iablokov V, Zaheer R, Colarusso P, Turner JR, MacNaughton WK Abstract Barrier dysfunction is a characteristic of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Understanding how the tight junction is modified to maintain barrier function may provide avenues for treatment of IBD. We have previously shown that the apical addition of serine proteases to intestinal epithelial cell lines causes a rapid and sustained increase in transepithelial electrical resistance (TER), but the mechanisms are unknown. We hypothesized that serine proteases increase barrier function through trafficking and insertion of tight junction proteins into the membrane, and this could enhance recovery of a disrupted monolayer after calcium switch or cytokine treatment. In the canine epithelial cell line, SCBN, we showed that matriptase, an endogenous serine protease, could potently increase TER. Using detergent solubility-based cell fractionation, we found that neither trypsin nor matriptase treatment changed levels of tight junction proteins at the membrane. In a fast calcium switch assay, serine proteases did not enhance the rate of recovery of the junction. In addition, serine proteases co...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research