Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2018; 24(9): 982-991
Published online Mar 7, 2018. doi: 10.3748/wjg.v24.i9.982
Dysregulation of PARP1 is involved in development of Barrett’s esophagus
Chao Zhang, Teng Ma, Tao Luo, Ang Li, Xiang Gao, Zhong-Gao Wang, Fei Li
Chao Zhang, Tao Luo, Ang Li, Xiang Gao, Zhong-Gao Wang, Fei Li, Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
Teng Ma, Beijing Institute of Radiation Medicine, Beijing 100053, China
Zhong-Gao Wang, Department of Gastroesophageal Reflux Disease, Second Artillery General Hospital of Chinese People’s Liberation Army, Beijing 100088, China
Author contributions: Zhang C, Ma T and Luo T are co-first authors; Zhang C, Ma T, Luo T and Li F designed and performed the research; Ma T, Li A and Gao X contributed the analytical tools; Zhang C and Luo T analyzed the data; Zhang C and Ma T wrote the manuscript; Luo T and Li F revised the manuscript; all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81470587; and Beijing Municipal Natural Science Foundation of China, No. 7162076.
Institutional review board statement: The study was reviewed and approved by the Second Artillery General Hospital of Chinese People’s Liberation Army and the Xuanwu Hospital Institutional Review Boards.
Institutional animal care and use committee statement: Approval from the animal care and use committee of Xuanwu Hospital was obtained for this study.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: There are no additional data available.
ARRIVE guidelines statement: This study meets the requirements of the ARRIVE guidelines.
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: Fei Li, MD, PhD, Chief Doctor, Professor, Department of General Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing 100053, China. feili35@126.com
Telephone: +86-10-83198731 Fax: +86-10-83198868
Received: December 9, 2017
Peer-review started: December 9, 2017
First decision: December 20, 2017
Revised: December 26, 2017
Accepted: January 23, 2018
Article in press: January 23, 2018
Published online: March 7, 2018
ARTICLE HIGHLIGHTS
Research background

Barrett’s esophagus is a major complication of gastro-esophageal reflux disease (GERD) and an important precursor lesion for the development of esophageal adenocarcinoma. However, the cellular and molecular mechanisms of Barrett’s metaplasia remain unclear. It has been demonstrated that poly(ADP-ribose) polymerases (PARPs)-associated ADP-ribosylation plays an important role in DNA damage and inflammatory response. Although PARP1-associated ADP-ribosylation has been examined both in vivo and in vitro, the function of PARP1 in esophageal epithelial cells and Barrett’s esophagus has not been illustrated.

Research motivation

In this study, the potential role of PARP1 and PARP1-related oxidative damage in Barrett’s esophagus was investigated.

Research objectives

The study investigated the potential role of PARP1 in oxidative damage in Barrett’s esophagus, which is urgent and essential for developing therapeutic targets.

Research methods

Expression of PARP1 gene was analyzed using microarray analysis in patient esophageal tissue samples. A Barrett’s esophagus mouse model was established to examine the esophageal morphological changes and molecular changes. qPCR was used to examine the PARP1 expression in cell lines after treatment with H2O2 and bile acids (pH 4). To evaluate the impact of PARP1 activity on cell survival and DNA damage response after oxidative stress, immunofluorescence staining, comet assay, and annexin V staining were used.

Research results

High expression of PARP1 was associated with Barrett’s esophagus. Positive staining for NF-κB, γH2AX, and poly(ADP-ribose) was observed in the mouse model of Barrett’s esophagus. Knockdown of PARP1 decreased the cell viability following treatment with H2O2 and bile acids (pH 4). We further demonstrated that PARP1 inhibition could increase the oxidative damage as demonstrated by an increase in the levels of H2O2, intracellular reactive oxygen species, oxidative DNA damage, double-strand breaks, and apoptosis.

Research conclusions

The dysfunction of PARP1 in esophageal epithelial cells increases the levels of reactive oxygen species and oxidative DNA damage, and downregulation of PARP1 or PARP1 inhibitor may be a potential therapeutic strategy for Barrett’s esophagus.

Research perspectives

This study will provide an example for investigating the relationship between the oxidative DNA damage and Barrett’s metaplasia, and the underlying role of the PARP1 in Barrett’s esophagus. The direction of the future research is to provide more evidence for developing novel strategies by targeting PARP1 in Barrett’s esophagus. In our future research, the PARP1-related downstream signaling pathway (inflammation or DNA damage) will be tested in Barrett’s esophagus epithelial cells or animal models to observe the inhibitory effect of PARP1.