title: MicroRNA-21 knockout improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tissue injury.
abstract: BACKGROUND
  MicroRNA-21 (miR-21) is overexpressed in most inflammatory diseases, but its physiological role in gut inflammation and tissue injury is poorly understood. The goal of this work is to understand the role of miR-21 in colitis and damage progression of intestine in a genetically modified murine model.
  
  
  METHODS
  Experimental colitis was induced in miR-21 KO and wild-type (WT) mice by 3.5% dextran sulphate sodium (DSS) administration for 7 days. Disease activity index(DAI), blood parameters, intestinal permeability, histopathologic injury, cytokine and chemokine production, and epithelial cells apoptosis were examined in colons of miR-21 KO and WT mice.
  
  
  RESULTS
  miR-21 was overexpressed in intestine of inflammatory bowel diseases (IBD) and acute intestinal obstruction (AIO) patients when compared with normal intestinal tissues. Likewise, miR-21 was up-regulated in colon of IL-10 KO mice when compared with control mice. WT mice rapidly lost weight and were moribund 5 days after treatment with 3.5% DSS, while miR-21 KO mice survived for at least 6 days. Elevated leukocytes and more severe histopathology were observed in WT mice when compared with miR-21 KO mice. Elevated levels of TNF-α and macrophage inflammatory protein-2(MIP-2) in colon culture supernatants from WT mice exhibited significant higher than miR-21 KO mice. Furthermore, CD3 and CD68 positive cells, intestinal permeability and apoptosis of epithelial cells were significantly increased in WT mice when compared with miR-21 KO mice. Finally, we found that miR-21 regulated the intestinal barrier function through modulating the expression of RhoB and CDC42.
  
  
  CONCLUSIONS
  Our results suggest that miR-21 is overexpressed in intestinal inflammation and tissue injury, while knockout of miR-21 in mice improve the survival rate in DSS-induced fatal colitis through protecting against inflammation and tissue injury. Therefore, attenuated expression of miR-21 in gut may prevent the onset or progression of inflammatory bowel disease in patients.
authors.affiliation: Department of General Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chenzhang
authors.initials: C
authors.lastname: Shi
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Hongqi
authors.initials: H
authors.lastname: Chen
authors.forename: Huazhong
authors.initials: H
authors.lastname: Han
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Yang
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.forename: Renyuan
authors.initials: R
authors.lastname: Gao
authors.forename: Huanlong
authors.initials: H
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000473:pathology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D016019:Survival Analysis
chemical_list: D016207:Cytokines; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D016264:Dextran Sulfate