title: CUEDC2 Protects Against Experimental Colitis and Suppresses Excessive Proliferation of Intestinal Mucosa.
abstract: BACKGROUND
  CUEDC2, a CUE domain-containing protein, is highly expressed in many tumors, which also may be associated with inflammation.
  
  
  OBJECTIVE
  In this study, we studied whether CUEDC2 plays a role in the progress of inflammatory bowel disease using CUEDC2 knockout (KO) mice and discussed the effects of CUEDC2 on cell proliferation in colonic mucosa.
  
  
  METHODS
  CUEDC2 KO mice were administered with drinking dextran sodium sulfate (DSS) to establish colitis mice model. At different time points after DSS administration, body weight and stool consistency of mice were graded. Cytokines in colon tissue such as IL-6 were measured by RT-PCR. NF-κB and STAT3 signaling pathways in colon tissue were assessed by western blotting. Besides, cell proliferation of intestinal mucosa was analyzed by immunohistochemical staining.
  
  
  RESULTS
  CUEDC2 alleviated the colonic inflammation, showing elevated body weight loss, worse diarrhea, and more severe colonic mucosal injury in CUEDC2 KO mice than WT mice. Moreover, pro-inflammatory cytokines such as IL-6, TNFα, COX2, and MIP2 were significantly elevated. In CUEDC2 KO mice, the NF-κB and STAT3 signaling pathways were increasingly activated in different stages of progression of the colonic inflammation, and the percentage of proliferating cells as indicated by Ki67, CyclinD1, and BrdU in the inflammatory tissues was significantly increased.
  
  
  CONCLUSIONS
  Our findings demonstrate that CUEDC2 plays an important role in protection from colonic inflammation, primarily by inhibiting the NF-κB and STAT3 signaling pathways and preventing excessive proliferation of the inflammatory epithelial cell.
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China. wangshaoxinby005@sina.com.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Laboratory, Navy General Hospital, Beijing, 100048, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Digestive, The Third Hospital of Peking University, Beijing, 100191, China.
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China.
authors.forename: Shanfeng
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Digestive, Navy General Hospital, Beijing, 100048, China. luckycui861@sina.com.
authors.forename: Lihong
authors.initials: L
authors.lastname: Cui
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D003106:Colon / Q000166:cytology*; D016264:Dextran Sulfate / Q000633:toxicity; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C576361:CUEDC2 protein, mouse; D016328:NF-kappa B; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016264:Dextran Sulfate
keywords: CUEDC2; Inflammation; Inflammatory bowel disease; Proliferation