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

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Abstract

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/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).

Conclusions

Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.

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Acknowledgments

TEM experiments were performed in the Central Laboratory of Osaka City University Medical School. We thank Mr. Hideki Nakagawa for technical support.

Funding

This work was supported by JSPS KAKENHI Grant Number JP24790659.

Author information

Authors and Affiliations

  1. Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Fumio Tanaka, Kazunari Tominaga, Yoshiko Fujikawa, Yasuaki Nagami, Noriko Kamata, Hirokazu Yamagami, Tetsuya Tanigawa, Masatsugu Shiba, Toshio Watanabe, Yasuhiro Fujiwara & Tetsuo Arakawa

  2. Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Fumio Tanaka

  3. SAMURAI GI Research Center, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Yoshiko Fujikawa

Authors
  1. Fumio Tanaka
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  2. Kazunari Tominaga
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  3. Yoshiko Fujikawa
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  4. Yasuaki Nagami
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  11. Tetsuo Arakawa
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Corresponding author

Correspondence to Kazunari Tominaga.

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Conflict of interest

Tetsuo Arakawa has participated in advisory committees for Otsuka Pharmaceutical Co. Ltd. and Eisai Co. Ltd. Yasuhiro Fujiwara has participated in advisory committees for Eisai Co. Ltd. All other authors declare that they have no conflicts of interest.

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Tanaka, F., Tominaga, K., Fujikawa, Y. et al. Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia. Dig Dis Sci 61, 3478–3485 (2016). https://doi.org/10.1007/s10620-016-4329-5

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  • DOI: https://doi.org/10.1007/s10620-016-4329-5

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