Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2016; 22(44): 9752-9764
Published online Nov 28, 2016. doi: 10.3748/wjg.v22.i44.9752
Transient receptor potential vanilloid 1-immunoreactive signals in murine enteric glial cells
Masahiro Yamamoto, Mitsue Nishiyama, Seiichi Iizuka, Shigeaki Suzuki, Norihiro Suzuki, Sadakazu Aiso, Jin Nakahara
Masahiro Yamamoto, Mitsue Nishiyama, Seiichi Iizuka, Tsumura Research Laboratories, Tsumura & Co., Ibaraki 300-1192, Japan
Shigeaki Suzuki, Norihiro Suzuki, Jin Nakahara, Department of Neurology, Keio University School of Medicine, Tokyo 160-0016, Japan
Sadakazu Aiso, Department of Anatomy, Keio University School of Medicine, Tokyo 160-0016, Japan
Author contributions: Yamamoto M conceived, designed and performed the in vitro cell culture experiments and immunocytochemistry, analyzed the data, and wrote the manuscript; Nishiyama M and Iizuka S bred the mice and prepared the specimens for further analyses; Suzuki S, Suzuki N and Aiso S contributed to experimental design and data analysis; Nakahara J conceived the study and designed and performed immunohistochemistry experiments; All authors read and approved the final version of the manuscript.
Institutional review board statement: This study was approved by the Institutional Review Boards of Keio University School of Medicine and Tsumura Research Laboratories.
Institutional animal care and use committee statement: All experimental procedures were performed according to the Guidelines for the Care and Use of Laboratory Animals of Tsumura & Co. Ethical approval (Approval #14-088) for the experimental procedures used in this study was obtained from the Laboratory Animal Committee of Tsumura & Co. All animal procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: Technical appendix and dataset are available from the corresponding author at
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Masahiro Yamamoto, PhD, Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami, Inashiki, Ibaraki 300-1192, Japan.
Telephone: +81-29-8893851 Fax: +81-29-8892158
Received: June 30, 2016
Peer-review started: July 1, 2016
First decision: August 29, 2016
Revised: September 2, 2016
Accepted: October 10, 2016
Article in press: October 10, 2016
Published online: November 28, 2016

To investigate the possible involvement of transient receptor potential vanilloid 1 (TRPV1) in maturation of enteric glial cells (EGCs).


Immunohistochemical and immunocytochemical techniques were used to analyze EGC markers in myenteric plexus (MP) as well as cultured MP cells and EGCs using TRPV1 knockout (KO) mice.


We detected TRPV1-immunoreactive signals in EGC in the MP of wild-type (WT) but not KO mice. Expression of glial fibrillary acidic protein (GFAP) immunoreactive signals was lower at postnatal day (PD) 6 in KO mice, though the difference was not clear at PD 13 and PD 21. When MP cells were isolated and cultured from isolated longitudinal muscle-MP preparation from WT and KO mice, the yield of KO EGC was lower than that of WT EGC, while the yield of KO and WT smooth muscle cells showed no difference. Addition of BCTC, a TRPV1 antagonist, to enriched EGC culture resulted in a decrease in the protein ratio of GFAP to S100B, another EGC/astrocyte-specific marker.


These results address the possibility that TRPV1 may be involved in the maturation of EGC, though further studies are necessary to validate this possibility.

Keywords: Enteric glial cells, Enteric nervous system, Glial fibrillary acidic protein, S100B, Smooth muscle cells

Core tip: We report that immunosignals of glial fibrillary acidic protein (GFAP) in myenteric ganglia in transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice are weaker than in wild-type mice in the early postnatal period, suggesting the possibility that the maturation of enteric glial cells (EGCs) might be retarded at least temporally in TRPV1 KO mice. Accordingly, in in vitro culture of isolated myenteric plexus cells/EGCs suggest that GFAP expression is affected by gene KO and an antagonist to TRPV1. The expression and function of TRPV1 in EGC merits further investigation.