Jagged-1 attenuates LPS-induced apoptosis and ROS in rat intestinal epithelial cells.

Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease that occurs in the colonic mucosa. This study investigated the role of the Notch pathway in affecting the pathogenesis of UC and regulating intestinal epithelial cell proliferation and apoptosis. Caspase-3 activity was measured and flow cytometry was used to detect reactive oxygen species (ROS) content and Ki-67 expression. Flow cytometry was applied to detect apoptosis, proliferation, and ROS content. Under LPS stimulation conditions, the IEC-6 cells were divided into 3 groups, including control, 5 and 10 μg/mL Jagged-1 protein pretreatment. The mRNA and protein expressions of Jagged-1, Notch1, Hes1, and OLFM4 in colon tissues were detected by real-time quantitative PCR (qRT-PCR) and Western blot. The ROS production, Ki-67 expression, and caspase-3 activity were significantly increased, and Jagged-1, Notch1, Hes1, and OLFM4 mRNA and protein levels were obviously elevated in the colon tissue of UC model rats compared with control. LPS treatment apparently up-regulated Jagged-1, Notch1, and OLFM4 expression in IEC-6 cells, resulting in marked enhancement in apoptosis and ROS generation, and reduction of proliferation. Administration of Jagged-1 before LPS stimulation further upregulated the expressions of Notch1 and OLFM4 in IEC cells, weakened apoptosis and ROS production, and alleviated the inhibitory effect of LPS on IEC-6 cell proliferation. UC lesions can activate the Notch signaling pathway in colon tissue, which may play a role in emergency repair. Upregulation of the Notch signaling pathway significantly reduced inflammatory stimuli-induced apoptosis and ROS generation in intestinal epithelial cells, resulting in increased cell proliferation.