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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice
Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, He Li, Wen-Feng Li, Guang-Bin Luo, Xin-Cheng Lu
Wan-Qin Liao, Ya-Lei Qi, Lin Wang, Xiao-Ming Dong, Tao Xu, Chao-Dong Ding, Rui Liu, Wei-Cheng Liang, Li-Ting Lu, Xin-Cheng Lu, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China
He Li, Wen-Feng Li, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
Guang-Bin Luo, Departments of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, United States
Author contributions: Qi YL, Wang L, Dong XM, Xu T and Ding CD performed the experiments; Liu R and Liang WC analyzed the data; Lu LT, Li H and Li WF provided technical assistances; Luo GB provided assistance in manuscript writing; Liao WQ and Lu XC designed the research and wrote the manuscript; all authors have read and approved the manuscript.
Supported by National Natural Science Foundation of China, No. 81101472 and No. 81472556 (to Liao W), and No. 81372490 (to Lu X); Zhejiang Provincial Natural Science Foundation, No. LZ14H160003 (to Lu X); Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (to Lu X); National Basic Research Program of China (973 Project), No. 2011CB504603; and Wenzhou Municipal Science and Technology Bureau Foundation, No. Y20110090 (to Li H).
Institutional review board statement: The study was reviewed and approved by the Wenzhou Medical University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Wenzhou Medical University (approval ID WYDW-20120081).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
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: Xin-Cheng Lu, Professor, School of Basic Medical Science, Wenzhou Medical University, Chashan Campus, Chashan University Town, Wenzhou 325027, Zhejiang Province, China.
xinchenglu@yahoo.com
Telephone: +86-577-88831350 Fax: +86-577-88831359
Received: April 9, 2015
Peer-review started: April 9, 2015
First decision: May 18, 2015
Revised: May 26, 2015
Accepted: July 3, 2015
Article in press: July 3, 2015
Published online: September 28, 2015
Processing time: 171 Days and 21.9 Hours
AIM: To investigate the effects of Recql5 deficiency on liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal).
METHODS: Liver injury was induced in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by histological, serum transaminases, and mortality analyses. Hepatocellular apoptosis was quantified by transferase dUTP nick end labeling assay and Western blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome P450 expression was analyzed by quantitative reverse transcription-PCR. Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot. Oxidative stress was evaluated by measuring malondialdehyde production and nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity.
RESULTS: Following LPS/D-Gal exposure, Recql5-deficient mice exhibited enhanced liver injury, as evidenced by more severe hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3 levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by increased γ-H2A.X levels. Inflammatory cytokine levels, neutrophil infiltration, and ERK phosphorylation were also significantly increased in the knockout mice. Additionally, Recql5-deficicent mice exhibited increased malondialdehyde production and elevated inducible nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression was significantly downregulated in Recql5-deficient mice after LPS/D-Gal treatment.
CONCLUSION: Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.
Core tip: Wild type and Recql5-deficient mice were intraperitoneally injected with lipopolysaccharide and D-galactosamine (LPS/D-Gal). The aim of the study was to explore the effects of Recql5 deficiency on LPS/D-Gal-induced liver injury. Our findings reveal that Recql5 protects against liver injury via inhibition of hepatocyte apoptosis and oxidative stress and regulation of hepatic CYP450 expression levels.
