Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2018; 24(44): 4989-5004
Published online Nov 28, 2018. doi: 10.3748/wjg.v24.i44.4989
Different distributions of interstitial cells of Cajal and platelet-derived growth factor receptor-α positive cells in colonic smooth muscle cell/interstitial cell of Cajal/platelet-derived growth factor receptor-α positive cell syncytium in mice
Chen Lu, Xu Huang, Hong-Li Lu, Shao-Hua Liu, Jing-Yu Zang, Yu-Jia Li, Jie Chen, Wen-Xie Xu
Chen Lu, Xu Huang, Hong-Li Lu, Yu-Jia Li, Wen-Xie Xu, Department of Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China
Shao-Hua Liu, Department of Anesthesiology, Ren Ji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China
Jing-Yu Zang, Jie Chen, Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Lu C designed and performed the majority of experiments; Huang X, Lu HL, and Liu SH contributed new reagents and analytic tools; Zang JY, Li YJ, and Chen J analyzed the data; Xu WX wrote and edited the manuscript.
Supported by The National Natural Science Foundation of China, No. 31671192 and No. 31571180; and Foundation of Xin Hua Hospital, No. JZPI201708.
Institutional review board statement: This research was approved by the Ethics Committee of Shanghai Jiao Tong University School of Medicine.
Institutional animal care and use committee statement: The protocol was approved by the Committee on the Ethics of Animal Experiments of Shanghai Jiao Tong University School of Medicine (Permit Number: Hu 686-2009).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data is available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines and prepared the manuscript accordingly.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Wen-Xie Xu, PhD, Professor, Department of Physiology, Shanghai Jiao Tong University School of Medicine, 800 Dongchuan Road, Shanghai 200240, China. wenxiexu@sjtu.edu.cn
Telephone: +86-21-34205639 Fax: +86-21-34205639
Received: August 24, 2018
Peer-review started: August 24, 2018
First decision: October 5, 2018
Revised: November 7, 2018
Accepted: November 7, 2018
Article in press: November 7, 2018
Published online: November 28, 2018
Processing time: 95 Days and 17.4 Hours
Abstract
AIM

To investigate the distribution and function of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in the proximal and distal colon.

METHODS

The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes (CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation (EFS)-induced inhibitory junction potentials (IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.

RESULTS

Treatment with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulation-induced nitric oxide (NO)/ICC-dependent slow IJPs (sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulation-induced purinergic/PDGFRα-dependent fast IJPs (fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1 (ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3 (SK3) in the distal colon were much higher.

CONCLUSION

The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.

Keywords: Interstitial cells of Cajal; Platelet-derived growth factor receptor-α positive cells; Smooth muscle cell/interstitial cell of Cajal/platelet-derived growth factor receptor-α positive cell syncytium; Nitric oxide; Purine

Core tip: The different distributions of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in the different parts of the colon result in a pressure gradient in the colon that propels the feces to the anus. Nitric oxide (NO) is mainly involved in the regulation of contraction through ICCs, and purine mainly participates in relaxation through PDGFRα+ cells. The regulation of the inhibitory transmitter NO and purine through the two kinds of interstitial cells (ICCs and PDGFRα+ cells) is very important for rhythmic colonic migrating motor complexes, which are the main driving force underlying colon transit.