Function And Mechanism Analysis Of Gpr35 In Inflammatory Bowel Disease

Intestinal inflammation is a high risk factor for the occurrence of colorectal cancer development,but its pathogenesis is unclear.It has important theoretical and clinical value for searching pathogenesis of enteritis and new therapeutic targets.G protein-coupled receptors on the cell membrane is the most family members of a class of membrane protein receptors,regulation of signaling pathways involved in a wide range of cell proliferation,differentiation,migration and other important biological processes,with the G protein-coupled receptor of many related diseases,G protein-coupled receptors become targets for drug therapy.GWAS assay have been found closely related to the development Gpr35 polymorphism and enteritis,but the mechanism and specific functions is not clear.By using the latest gene knockout technology CRISPR/Cas9,this project build Gpr35 global knockout mice and found Gpr35 deficiency does not affect the normal intestinal growth and development.However,Gpr35 knockout mice are not sensitive to acute enteritis,indicating Gpr35 can play a protective role in the DSS-induced acute colitis model.In bone marrow transplantation experiments also proved that,because Gpr35 gene in acute enteritis intestinal epithelium caused by lack of insensitive,which has nothing to do with the immune system.ERK and AKT signaling pathway were detected by Western Blot after inflammation of the intestine of mice,we found Gpr35 deficiency made the tissues protein AKT signaling phosphorylated stronger.By building human enteritis common mutant Gpr35,using in vitro determination of calcium signaling,which also occurred mutations can indeed Gpr35 excessive activation of downstream signaling.Therefore,Gpr35 knockout mice have not yet been reported,we first generated Gpr35 knockout mice,this study found that Gpr35 genes by affecting intestinal epithelial cell homeostasis can promote the development of colitis.