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
Abstract
AIM

To investigate the potential role of poly(ADP-ribose) polymerase 1 (PARP1) in the development of Barrett’s esophagus (BE).

METHODS

A BE mouse model was established to examine the esophageal morphological changes and molecular changes. Microarray analysis was performed to compare the gene expression profiles between BE patients and healthy controls. qPCR was used to examine the PARP1 expression in cell lines after treatment with H2O2 and bile acids (pH 4). Immunofluorescence staining, comet assay, and annexin V staining were used to evaluate the impact of PARP1 activity on cell survival and DNA damage response after oxidative stress.

RESULTS

The gene expression profile in normal and BE esophageal epithelial cells showed that PARP1, the major poly(ADP-ribose) polymerase, was overexpressed in BE. In the mouse model of BE, positive staining for NF-κB, γH2AX, and poly(ADP-ribose) (PAR) was observed. H2O2 and bile acids (pH 4) increased the PARP1 mRNA expression level in normal esophageal epithelial cells. Using shRNA-PARP1 to suppress PARP1 activity decreased the cell viability after treatment with H2O2 and bile acids (pH 4), and increased the oxidative damage as demonstrated by an increase in the levels of H2O2, intracellular reactive oxygen species (ROS), oxidative DNA damage, double-strand breaks, and apoptosis (P < 0.01).

CONCLUSION

The dysfunction of PARP1 in esophageal epithelial cells increases the levels of ROS and oxidative DNA damage, which could be common risk factors for BE and esophageal adenocarcinoma.

Keywords: PARP1, Barrett’s esophagus, DNA repair, Oxidative damage, Bile acids

Core tip: In this study, we compared the gene expression profile in normal esophagus and Barrett’s esophagus (BE), and found that poly(ADP-ribose) polymerase 1 (PARP1) was overexpressed in BE. In a BE model, positive staining for NF-κB, γH2AX, and PAR was observed. H2O2 and bile acids (pH 4) increased the PARP1 mRNA expression level in normal esophageal epithelial cells. PARP1 inhibition could decrease the cell viability after bile acids treatment, and increased the oxidative damage, double-strand breaks, and apoptosis. Thus, our study demonstrates a novel molecular mechanism for the role of PARP1 in the process of Barrett’s metaplasia, which sheds a potential therapeutic role for PARP1 inhibitor in BE.