Role of Csk in intestinal epithelial barrier function and protection against colitis.

Intestinal epithelial cells (IECs) play a pivotal role in the maintenance of the integrity and barrier function of the intestinal epithelium. Dysfunctions of IECs are thought to participate in the disruption of the intestinal epithelial barrier, resulting in gastrointestinal diseases, such as colitis and colorectal cancer. Here we show that IEC-specific COOH-terminal Src kinase (Csk)-deficient mice (Csk CKO mice) manifested the increased susceptibility to dextran sodium sulfate (DSS)-induced colitis, a model of inflammatory bowel disease. DSS-treated Csk CKO mice also exhibited the significantly elevated intestinal permeability. Following DSS treatment, Csk CKO mice exhibited the higher proliferative activity of colonic epithelial cells and the increased number of apoptotic cells in the colon compared with that apparent for control mice. Moreover, the abundance of the tight junction protein occludin, which regulates cell-cell adhesion as well as epithelial permeability, was markedly reduced in the colon of DSS-treated Csk CKO mice. These results thus suggest that Csk in IECs plays important roles in the regulation of the intestinal epithelial barrier function and protection against colitis.