CD47 Regulates Self-renewal And Proliferation Of Intestinal Epithelial Cells Through Targeting OSKM Factors

Inflammatory bowel disease(IBD)is a non-specific autoimmune disease that occurs in the intestinal tract and has the characteristics of chronic and easy to relapse.The pathogenesis of IBD is very complex and is often thought to be caused by combination of various genetic and environmental factors that activate immune cells and abnormal immune responses.Regardless of factors such as environment or immunity,the most essential causes of inflammatory bowel disease is the damage to intestinal epithelial cells.Therefore,how to repair and renew damaged intestinal epithelial cells is a key issue for IBD.For this reason,this thesis is based on the repair of intestinal epithelial cells,looks for the key proteins that can promote the self-renewal of intestinal epithelial cells,and study the mechanism,in order to provide a new target for the treatment of IBD.First of all,this thesis uses bioinformatics methods to screen CD47 is an important protein associated with IBD.On this basis,we found that CD47 expression was significantly up-regulated in the intestinal epithelium of patients with ulcerative colitis compared with normal controls.Further,using the mouse model of ulcerative colitis,we found that the expression of CD47 in the intestinal epithelium was significantly upregulated during the development and progression of enteritis,suggesting that CD47 may be involved in the occurrence and development of ulcerative colitis in mice.In order to clarify the relationship between CD47 and ulcerative colitis,we further used CD47 knockout mice to make DSS model and found that CD47-deficient mice develop slower inflammation than wild-type mice.Further,we found that CD47 may affect the repair and proliferation of intestinal epithelial cells by regulating the four factors Oct4,Sox2,Klf4,and cMyc(OSKM)by using bioinformatics analysis,thereby regulating the occurrence and development of ulcerative colitis.To verify the specific mechanism of CD47 regulating the proliferation and repair of intestinal epithelial cells,we performed CD47 overexpression and inhibition experiments in mouse colon cancer cell line CT26 cells,and confirmed whether CD47 regulates the proliferation and repair of intestinal epithelial cells through the four OSKMs.The results showed that overexpression of CD47 in CT26 significantly inhibited the proliferation and repair of injury-inducing cells,and the expression of the four OSKM factors was significantly down-regulated;whereas,siRNA inhibited the expression of endogenous CD47,and the expression of these four factors was significantly increased.And the cell proliferation of siRNA group was also significantly higher than of the overexpression group.Therefore,CD47 regulates the repair of intestinal epithelial cells by regulating the expression of four OSKM factors,Sox2,Klf4,cMyc,and Oct4.