title: Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia.
abstract: In patients with functional dyspepsia (FD), mild duodenal inflammation correlates with increased mucosal permeability. Enteric glial cells can produce glial cell line-derived neurotrophic factor (GDNF) to repair disrupted epithelial barrier function.
  
  
  
  We examined the role of duodenal GDNF in FD pathophysiology and its association with dyspeptic symptoms.
  
  
  
  Duodenal biopsies taken from FD patients and control subjects were used for analysis. GDNF protein expression and localization were examined. Cellular infiltration of eosinophils and mast cells was measured. We also examined the intercellular space between the adjacent epithelial cells at the apical junction complex using transmission electron microscopy.
  
  
  
  In FD patients, expression of GDNF protein was significantly increased compared with controls, 107.3 (95.3-136.7) versus 49.3 (38.0-72.6) pg/mg protein (median (interquartile range), p = 0.006), respectively. GDNF was localized in enteric glial cells, eosinophils, and epithelial cells. The number of eosinophils was significantly greater in FD patients than in controls, 1039 (923-1181) versus 553 (479-598) cells/mm2(p = 0.021), respectively. The intercellular space was dilated at the adherent junction in FD patients compared to control patients, 32.4 (29.8-34.8) versus 22.0 (19.9-26.1) nm (p = 0.002), respectively. Intercellular distance positively correlated with the frequency of postprandial fullness and early satiation (p = 0.001, r = 0.837 and p = 0.009, r = 0.693, respectively). Expression of GDNF correlated with epigastric burning (p = 0.041, r = 0.552).
  
  
  
  Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.|Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan. tomy@med.osaka-cu.ac.jp.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.|SAMURAI GI Research Center, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fujikawa
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nagami
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamata
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Shiba
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000328:Adult; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D004415:Dyspepsia / Q000378:metabolism* / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008407:Mast Cells / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D010539:Permeability
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor
keywords: Dyspepsia; Enteric nervous system; Glial cell line-derived neurotrophic factor; Upper gastrointestinal tract