Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 21, 2013; 19(23): 3583-3595
Published online Jun 21, 2013. doi: 10.3748/wjg.v19.i23.3583
Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism
Zhong-Yang Shen, Jing Zhang, Hong-Li Song, Wei-Ping Zheng
Zhong-Yang Shen, Jing Zhang, Hong-Li Song, Wei-Ping Zheng, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China
Author contributions: Song HL and Shen ZY designed the research, analyzed and interpreted the data, and wrote the manuscript; Shen ZY, Zheng WP and Zhang J performed the research; Song HL and Zheng WP analyzed the data; all authors have read and approved the final manuscript.
Supported by Natural Science Foundation of China, No. 81270528; the Natural Science Foundation of Tianjin, No. 08JCYBJC08400, No. 11JCZDJC27800 and No. 12JCZDJC25200; the Technology Foundation of Health Bureau in Tianjin, No. 2011KY11
Correspondence to: Hong-Li Song, MD, PhD, Professor of Medicine, Department of Organ Transplantation, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300192, China. hlsong26@163.com
Telephone: +86-22-23626928 Fax: +86-22-23626622
Received: December 30, 2012
Revised: March 21, 2013
Accepted: April 3, 2013
Published online: June 21, 2013
Processing time: 171 Days and 18.7 Hours
Abstract

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury.

METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.

RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption.

CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.

Keywords: Bone marrow mesenchymal stem cells; Zona occludens 1; Ischemia-reperfusion injury; Intestinal mucosa; Tumor necrosis factor-α

Core tip: Intestinal ischemia/reperfusion (I/R) injury is clinically important. Bone-marrow mesenchymal stem cells (BM MSCs) can protect against I/R injury; however, the mechanism is unclear. This study demonstrates that submucosal infusion of BM MSCs decreased intestinal permeability and preserved intestinal mechanical barrier function after I/R injury in rats, via a mechanism linked to reduced serum tumor necrosis factor (TNF)-α levels and increased expression of the intestinal tight junction protein zona occludens 1. Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.