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Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low‐grade inflammation in ulcerative colitis
Author(s) -
Tada Yasumasa,
Ishihara Shunji,
Kawashima Kousaku,
Fukuba Nobuhiko,
Sonoyama Hiroki,
Kusunoki Ryusaku,
Oka Akihiko,
Mishima Yoshiyuki,
Oshima Naoki,
Moriyama Ichiro,
Yuki Takafumi,
Ishikawa Noriyoshi,
Araki Asuka,
Harada Yuji,
Maruyama Riruke,
Kinoshita Yoshikazu
Publication year - 2016
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13268
Subject(s) - medicine , colitis , inflammatory bowel disease , ulcerative colitis , intestinal mucosa , serotonin transporter , inflammation , gastroenterology , serotonin plasma membrane transport proteins , pathogenesis , colonoscopy , pathology , serotonin , colorectal cancer , disease , cancer , receptor
Background and Aim 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.