title: Heterogeneous Nuclear Ribonucleoprotein A1 Improves the Intestinal Injury by Regulating Apoptosis Through Trefoil Factor 2 in Mice with Anti-CD3-induced Enteritis.
abstract: BACKGROUND
  The role of hnRNP A1 in the onset of intestinal inflammation remains unclear. This study investigated the function of hnRNP A1 in mice enteritis models.
  
  
  METHODS
  C57Bl6/J mice were intraperitoneally injected with anti-CD3 antibodies to develop enteritis. In the DSS-induced colitis group, the mice were allowed free access to 3% DSS solution in their drinking water for 5 days. 3H-mannitol flux and complementary DNA array tests were used to assess the intestinal barrier function and messenger RNA (mRNA) expression, respectively. Real-time PCR was performed after immunoprecipitation with anti-hnRNP antibodies to determine the specific mRNA binding of hnRNP A1.
  
  
  RESULTS
  The hnRNP A1 expression was increased in the intestine of the mouse at 24 hours after treatment with anti-CD3 antibodies and 5 days after starting DSS administration. Small interfering RNA (siRNA) against hnRNP A1 exacerbated the intestinal injuries in both models. According to the microarray analysis, trefoil factor 2 (TFF2) was identified as a candidate molecule targeted by hnRNP A1 in the anti-CD3 antibody-induced enteritis group. Moreover, the binding between hnRNP A1 and TFF2 mRNA significantly increased in the enteritis mice, and the administration of siRNA against either hnRNP A1 or TFF2 exacerbated the degree of intestinal injury. In the DSS-induced colitis group, treatment with the siRNA of hnRNP A1 worsened the intestinal injury, while the expression of TFF3 did not change.
  
  
  CONCLUSIONS
  hnRNP A1 improves intestinal injury in anti-CD3 antibody-induced enteritis mice through the upregulation of TFF2, which regulates apoptosis and enhances epithelial restoration, whereas this molecule ameliorates DSS-induced colitis through a different pathway.
authors.affiliation: *Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan; and †Department of Gastroenterology, International Health and Science University Hospital, Nasushiobara, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Konishi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ueno
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Inaba
authors.forename: Kentaro
authors.initials: K
authors.lastname: Moriichi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ikuta
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ohtake
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004751:Enteritis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000096:biosynthesis / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000071164:Trefoil Factor-2
chemical_list: D017252:CD3 Complex; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C000619657:Hnrnpa1 protein, mouse; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012333:RNA, Messenger; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2