Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2016; 22(46): 10131-10139
Published online Dec 14, 2016. doi: 10.3748/wjg.v22.i46.10131
Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus
Kyung Sik Park, Kwang Bum Cho, Il Seon Hwang, Jae Hyung Park, Byung Ik Jang, Kyeong Ok Kim, Sung Woo Jeon, Eun Soo Kim, Chang Sik Park, Joong Goo Kwon
Kyung Sik Park, Kwang Bum Cho, Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, South Korea
Il Seon Hwang, Department of Pathology, Keimyung University School of Medicine, Daegu 42601, South Korea
Jae Hyung Park, Department of Physiology, Keimyung University School of Medicine, Daegu 42601, South Korea
Byung Ik Jang, Kyeong Ok Kim, Department of Internal Medicine, Youngnam University College of Medicine, Daegu 42415, South Korea
Sung Woo Jeon, Eun Soo Kim, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 41944, South Korea
Chang Sik Park, Department of Advanced Materials Convergence, Korea Institute of Ceramic Engineering and Technology, Jinju City, Gyeongnam 52851, South Korea
Joong Goo Kwon, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu 42471, South Korea
Author contributions: Park KS and Kwon JG designed this study; assistance in recruiting participants and data collection was provided by Cho KB, Jang BI, Kim KO, Jeon SW and Kim ES; Hwang IS, Park JH and Park CS participated in the interpretation of pathologic specimens and were responsible for the analysis of data; all authors contributed to manuscript revision.
Supported by the National Research Foundation of Korea Grant funded by the Korean Government, No. 2014R1A5A2010008.
Institutional review board statement: This study was approved by Keimyung University School of Medicine/Dongsan Hospital Institutional Review Board.
Conflict-of-interest statement: Not declared.
Data sharing statement: No additional data are available.
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/
Correspondence to: Dr. Joong Goo Kwon, Professor, Department of Internal Medicine, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-Gu, Daegu 42471, South Korea. kwonjg@cu.ac.kr
Telephone: +82-53-6504215 Fax: +82-53-6214487
Received: June 21, 2016
Peer-review started: June 23, 2016
First decision: September 21, 2016
Revised: October 1, 2016
Accepted: October 30, 2016
Article in press: October 31, 2016
Published online: December 14, 2016
Abstract
AIM

To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus (DM).

METHODS

Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson’s Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), neurokinin-1 (NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha, (PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also conducted.

RESULTS

Twenty-six controls and 35 diabetic patients (21 short-duration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index (BMI) (higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group (P < 0.01). On immunohistochemical staining, c-Kit- and PDGFRα-positive immunoreactivity were significantly decreased in the DM group compared with the control group (P < 0.05). There were no statistically significant differences in PGP9.5, nNOS, VIP, and neurokinin 1 expression. On immunofluorescent staining, cellularity of interstitial cells of Cajal (ICC) was observed to decrease with increasing duration of DM.

CONCLUSION

Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

Keywords: Diabetes mellitus, Interstitial cells of Cajal, Fibroblast-like cell, Gastroparesis, Enteric nerve system

Core tip: In this study, we discovered that increased intercellular fibrosis, loss of interstitial cells of Cajal, and loss of fibroblast-like cells are found in the smooth muscle of diabetes mellitus (DM) patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.