title: Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low-grade inflammation in ulcerative colitis.
abstract: OBJECTIVE
  The serotonin reuptake transporter (SERT) terminates serotonin activity by removing it from interstitial space. Downregulated colonic SERT expression has been reported in irritable bowel disease (IBS), and symptoms resembling IBS occur in cases of inflammatory bowel disease (IBD) in remission; thus, a common pathogenesis for IBS and IBD is possible. However, little is known regarding SERT expression in colonic mucosa of IBD patients during healing.
  
  
  METHODS
  Twenty-two ulcerative colitis (UC) patients underwent colonoscopy examinations, during which inflamed mucosa was distinguished from that undergoing healing. Healing mucosa was classified into regular and irregular vessel patterns by narrowband imaging magnifying colonoscopy. Expressions of SERT and various inflammation-related genes in biopsy samples were assessed using a polymerase chain reaction array system and real-time polymerase chain reaction. Colitis model mice were established by administration of dextran sodium sulfate or transfer of CD4(+) T cells isolated from SAMP1 mice, then time-course changes of SERT and inflammatory gene expressions were observed in colonic mucosa.
  
  
  RESULTS
  In UC patients, SERT expression in inflamed mucosa was significantly lower than in healing mucosa. SERT expression was decreased in healing mucosa with an irregular vessel pattern with mildly increased levels of inflammatory gene expression. In mice, SERT expression was suppressed in inflamed mucosa and continuously observed with low-grade mucosal inflammation during colitis healing.
  
  
  CONCLUSIONS
  Sserotonin reuptake transporter expression is downregulated in healing colonic mucosa of UC patients and that suppression may be dependent on the presence of remaining low-grade colonic inflammation.
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Kawashima
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Fukuba
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sonoyama
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Kusunoki
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Oka
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mishima
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshima
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.|Cancer Center, Shimane University Hospital, Izumo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Moriyama
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yuki
authors.affiliation: Department of Organ Pathology, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Ishikawa
authors.affiliation: Department of Organ Pathology, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Araki
authors.affiliation: Department of Pathology Laboratory, Shimane University Hospital, Izumo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Organ Pathology, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Riruke
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Internal Medicine II, Shimane University Faculty of Medicine, Matsue, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003113:Colonoscopy; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics; D014945:Wound Healing
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D016264:Dextran Sulfate; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase
keywords: inflammatory bowel disease; irritable bowel syndrome; mucosal healing; serotonin; serotonin reuptake transporter; ulcerative colitis