Randomized Controlled Trial
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2014; 20(25): 8260-8267
Published online Jul 7, 2014. doi: 10.3748/wjg.v20.i25.8260
ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats
Xia Chen, Xiang-Sheng Fu, Chang-Ping Li, Hong-Xian Zhao
Xia Chen, Xiang-Sheng Fu, Chang-Ping Li, Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Sichuan Province, China
Hong-Xian Zhao, Department of Histology and Embryology, Luzhou Medical College, Luzhou 646000, Sichuan Province, China
Author contributions: Chen X and Zhao HX performed the experiments and data analysis, and wrote the manuscript; Fu XS provided analytical tools, intellectual input and advice; Li CP contributed to the conceptual design; all the authors have read and approved the final manuscript.
Supported by A grant from the Department of Health, Sichuan Province, China, No. 070267
Correspondence to: Hong-Xian Zhao, MD, Associate Professor, Department of Histology and Embryology, Luzhou Medical College, No. 25, Taiping Street, Luzhou 646000, Sichuan Province, China. 970217858@qq.com
Telephone: +86-830-3161222 Fax: +86-830-3161222
Received: January 1, 2014
Revised: March 4, 2014
Accepted: April 5, 2014
Published online: July 7, 2014
Processing time: 182 Days and 22.4 Hours
Abstract

AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis.

METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry.

RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins.

CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis.

Keywords: Diabetic gastroparesis; Apoptosis; Endoplasmic reticulum stress; glucose-regulated protein 78 kD; Caspase-12

Core tip: Endoplasmic reticulum stress and/or ER stress-induced apoptosis in the etiology of diabetic gastroparesis (DGP) remain unclear. This study focuses on the muscle injury caused by ER stress in rats with DGP. We found that apoptosis of gastric smooth muscle cells (SMCs) increased in diabetic rats in addition to increased expression of the ER stress marker, glucose-regulated protein 78, and the ER-specific apoptosis mediator, caspase-12. This is the first study to demonstrate that ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats.