Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia

• Published in: Digestive diseases and sciences Vol. 61; no. 12; pp. 3478 - 3485
• Main Authors: Tanaka, Fumio, Tominaga, Kazunari, Fujikawa, Yoshiko, Nagami, Yasuaki, Kamata, Noriko, Yamagami, Hirokazu, Tanigawa, Tetsuya, Shiba, Masatsugu, Watanabe, Toshio, Fujiwara, Yasuhiro, Arakawa, Tetsuo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2016; Springer; Springer Nature B.V
• Subjects: Adult; Analysis; Biochemistry; Duodenum - metabolism; Duodenum - pathology; Duodenum - ultrastructure; Dyspepsia; Dyspepsia - metabolism; Dyspepsia - pathology; Eosinophils - pathology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelial Cells - ultrastructure; Ethylenediaminetetraacetic acid; Female; Gastroenterology; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Hepatology; Humans; Inflammation; Intercellular Junctions - ultrastructure; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestinal Mucosa - ultrastructure; Male; Mast Cells - pathology; Medicine; Medicine & Public Health; Microscopy, Electron, Transmission; Middle Aged; Neuroglia - metabolism; Neuroglia - pathology; Oncology; Original Article; Permeability; Transplant Surgery; Enteric nervous system; Glial cell line-derived neurotrophic factor; Dyspepsia; Upper gastrointestinal tract
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-016-4329-5

Background 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. Aims We examined the role of duodenal GDNF in FD pathophysiology and its association with dyspeptic symptoms. Methods 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. Results 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/mm 2 ( 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). Conclusions Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.