Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jun 27, 2023; 15(6): 1068-1079
Published online Jun 27, 2023. doi: 10.4240/wjgs.v15.i6.1068
Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis
Fan Ding, Run Guo, Fang Chen, Li-Ping Liu, Zheng-Yu Cui, Yi-Xing Wang, Gang Zhao, Hai Hu
Fan Ding, Gang Zhao, Hai Hu, Center of Gallbladder Disease, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
Fan Ding, Gang Zhao, Hai Hu, Institute of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200331, China
Run Guo, Fang Chen, Li-Ping Liu, Department of Ultrasonography, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
Zheng-Yu Cui, Yi-Xing Wang, Department of Internal Medicine of Traditional Chinese Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
Author contributions: Ding F and Guo R performed experiments; Hu H, Zhao G, and Wang YX designed the study; Cui ZY performed data analysis; Chen F and Liu LP drafted the manuscript; all authors reviewed the final manuscript.
Supported by the Pudong New Area Clinical Traditional Chinese Medicine of Top Discipline Project, No. PDZY-2018-0603 and the Featured Clinical Discipline Project of Shanghai Pudong, No. PWYts2021-06.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the East Hospital of Tongji University (approval No. 2020-12-102).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai Hu, MD, PhD, Director, Center of Gallbladder Disease, Shanghai East Hospital, School of Medicine, Tongji University, No. 150 Jimo Road, Shanghai 200120, China. huhailc@sina.com
Received: December 29, 2022
Peer-review started: December 29, 2022
First decision: February 20, 2023
Revised: February 21, 2023
Accepted: April 14, 2023
Article in press: April 14, 2023
Published online: June 27, 2023
Processing time: 168 Days and 0.9 Hours
ARTICLE HIGHLIGHTS
Research background

Acute cholecystitis (AC) is a common disease with gallbladder dysmotility. Interstitial cells of Cajal (ICCs) damage and loss in the biliary system have been associated with various biliary systemic diseases. However, it remains unclear if or how the pathogenesis affects ICCs morphology, density, distribution, slow waves (SW), and function in gallbladder during AC.

Research motivation

Decreased gallbladder contractile function is an important causative factor in AC. ICCs presented significant pathological changes during AC in various animal and clinical studies. Therefore, ICCs may act as important regulators of gallbladder contractile function.

Research objectives

To investigate the origin of SW in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC. We hypothesized that ICCs are the origin of SW in the gallbladder, and the impaired leads to the decrease in gallbladder contractile function, which ultimately aggravates the AC.

Research methods

Common bile duct ligation is a common model of AC. Guinea pigs were randomly allocated to four groups: Normal control (NC), AC12h, AC24h, and AC48h. H&E and Masson-stained gallbladder tissues were scored for inflammatory changes. Methylene blue with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility. Then ICCs pathological changes alterations were estimated using immunohistochemistry and TEM. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot.

Research results

Gallbladder strips treated MB with light resulted in the decrease in gallbladder SW frequency and contractility. Compared with the NC group, The frequency of SW, gallbladder contractility, the density and ultrastructure of ICCs were significantly impaired in AC groups. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.

Research conclusions

This study indicated that ICCs may act as pacemaker cells for the SW of the gallbladder. In acute inflammation stage of AC, impaired ICCs resulted in the reduction of the SW and gallbladder motility deficiency. Then, the decrease of CCKAR and gap junction leads to the further decrease in gallbladder contractility and electrical conductivity, and eventually result in AC.

Research perspectives

This study did not completely destroy ICCs in the gallbladder tissue. The pacing mechanism of ICCs has also not been deeply investigated. These will be examined in the future study.