PMID- 26984549
OWN - NLM
STAT- MEDLINE
DCOM- 20170531
LR  - 20181113
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Linking)
VI  - 51
IP  - 11
DP  - 2016 Nov
TI  - Serotonin disrupts esophageal mucosal integrity: an investigation using a 
      stratified squamous epithelial model.
PG  - 1040-1049
AB  - BACKGROUND: Serotonin regulates gastrointestinal function, and mast cells are a 
      potential nonneuronal source of serotonin in the esophagus. Tight junction (TJ) 
      proteins in the esophageal epithelium contribute to the barrier function, and the 
      serotonin signaling pathway may contribute to epithelial leakage in 
      gastroesophageal reflux disease. Therefore, the aim of this study was to 
      investigate the role of serotonin on barrier function, TJ proteins, and related 
      signaling pathways. METHODS: Normal primary human esophageal epithelial cells 
      were cultured with use of an air-liquid interface system. Serotonin was added to 
      the basolateral compartment, and transepithelial electrical resistance (TEER) was 
      measured. The expression of TJ proteins and serotonin receptor 7 (5-HT(7)) was 
      assessed by Western blotting. The involvement of 5-HT(7) was assessed with use of 
      an antagonist and an agonist. The underlying cellular signaling pathways were 
      examined with use of specific blockers. RESULTS: Serotonin decreased TEER and 
      reduced the expression of TJ proteins ZO-1, occludin, and claudin 1, but not 
      claudin 4. A 5-HT(7) antagonist blocked the serotonin-induced decrease in TEER, 
      and a 5-HT(7) agonist decreased TEER. Inhibition of p38 mitogen-activated protein 
      kinase (MAPK) reduced the serotonin-induced decrease in TEER. Inhibition of p38 
      MAPK blocked the decrease of ZO-1 levels, whereas extracellular-signal-regulated 
      kinase (ERK) inhibition blocked the decrease in occludin levels. Cell signaling 
      pathway inhibitors had no effect on serotonin-induced alterations in claudin 1 
      and claudin 4 levels. Serotonin induced phosphorylation of p38 MAPK and ERK, and 
      a 5-HT(7) antagonist partially blocked serotonin-induced phosphorylation of p38 
      MAPK but not that of ERK. CONCLUSIONS: Serotonin disrupted esophageal squamous 
      epithelial barrier function by modulating the levels of TJ proteins. Serotonin 
      signaling pathways may mediate the pathogenesis of gastroesophageal reflux 
      disease.
FAU - Wu, Liping
AU  - Wu L
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
AD  - Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, 
      China.
FAU - Oshima, Tadayuki
AU  - Oshima T
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 
      t-oshima@hyo-med.ac.jp.
FAU - Tomita, Toshihiko
AU  - Tomita T
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Ohda, Yoshio
AU  - Ohda Y
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Fukui, Hirokazu
AU  - Fukui H
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Watari, Jiro
AU  - Watari J
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
FAU - Miwa, Hiroto
AU  - Miwa H
AD  - Division of Gastroenterology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160316
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Tight Junction Proteins)
RN  - 0 (serotonin 7 receptor)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Electric Impedance
MH  - Epithelial Cells/drug effects/metabolism
MH  - Esophageal Mucosa/cytology/*drug effects/metabolism
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Receptors, Serotonin/metabolism/physiology
MH  - Serotonin/administration & dosage/*pharmacology
MH  - Signal Transduction/drug effects
MH  - Tight Junction Proteins/drug effects/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/drug effects/metabolism
OTO - NOTNLM
OT  - Air-liquid interface
OT  - Serotonin
OT  - Stratified epithelium
OT  - Tight junction protein
OT  - Transepithelial electrical resistance
EDAT- 2016/10/28 06:00
MHDA- 2017/06/01 06:00
CRDT- 2016/03/18 06:00
PHST- 2015/12/08 00:00 [received]
PHST- 2016/03/06 00:00 [accepted]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2017/06/01 06:00 [medline]
PHST- 2016/03/18 06:00 [entrez]
AID - 10.1007/s00535-016-1195-z [pii]
AID - 10.1007/s00535-016-1195-z [doi]
PST - ppublish
SO  - J Gastroenterol. 2016 Nov;51(11):1040-1049. doi: 10.1007/s00535-016-1195-z. Epub 
      2016 Mar 16.