Role And Mechanism Of Eftud2 In The Regulation Of UC

Background & Aims: Ulcerative Colitis(UC)is an inflammatory bowel disease restricted to the colonic mucosa.The disease is characterized by remitting and relapsing,and the mechanism of the disease is still unknown.The colonic epithelial cells defines a physical barrier between the inside of the body and the environment.The maintenance of this border relies on the multifunction of intestinal epithelial cells(IEC),including the production of cytokines and secretion of antimicrobial peptides.Long-lasting changes in the function of epithelial cells have been reported in quiescent UC.The Tolllike receptors(TLRs)is a family of pattern-recognition receptors expressed on IEC that critical for the initiation of inflammatory and immune defense responses.In the UC/CAC mice model according to our previous research,protein expression of Eftud2 significantly upregulate.Eftud2,a core component of U5 snRNPs,plays a pivotal role in RNA splicing.Eftud2 is identified,as a novel regulator of innate immunity,by alternate splicing of the MyD88 signaling adaptor to modulate the extent of the innate immune response.The aim of this dissertation is to identify the function of Eftud2 in the regulation of epithelial cell fate and to investigate the role of epithelial Eftud2 in UC progress.Methods: With the use of Cre/Loxp system,we generated mice lacking Eftud2 exclusively in the epithelial cells.In vitro,the IEC was isolated from gene knockout(KO)and wild-type(WT)mice.ELISA was used to detect the release of several cytokines from epithelial cells stimulated by LPS and NF-?B signaling pathway were determined by Western Blot.In vivo,cell proliferation and the function of physical barrier in epithelial cells from KO and WT mice were detected under homeostatic conditions.UC was induced by DSS by adding to mice's drinking water,signs of colitis and histology were than analyzed.Results: Epithelial cells isolated from KO and WT mice release similar level of inflammatory cytokines after LPS stimulation,including IL-1??IL-6?IL-17 A and TNF-?.The phosphorylation of p65,subunit of NF-?B,shows no difference compared KO to WT mice.According to histology results,Eftud2 has no effect on epithelial proliferation.Acute colitis was induced by DSS instillation in KO and WT mice.The ablation led no significant effect on signs of colitis,including weight loss,mortality,food intake,colon longth,colon damage and oedema.