Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2019; 25(9): 1067-1079
Published online Mar 7, 2019. doi: 10.3748/wjg.v25.i9.1067
Integrated network analysis of transcriptomic and protein-protein interaction data in taurine-treated hepatic stellate cells
Xing-Qiu Liang, Jian Liang, Xiao-Fang Zhao, Xin-Yuan Wang, Xin Deng
Xing-Qiu Liang, Xiao-Fang Zhao, Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
Jian Liang, College of Medical, Guangxi University, Nanning 530004, Guangxi Zhuang Autonomous Region, China
Xin-Yuan Wang, Xin Deng, School of Basic Sciences, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China
Author contributions: Deng X and Liang XQ contributed equally to the study, performed the majority of experiments, and analyzed the data; Liang XQ wrote the paper; Zhao XF and Wang XY performed the treatment of HSCs; Liang J designed and coordinated the research.
Supported by the National Natural Science Foundation of China, No. 81360595 and No. 81860790; Guangxi Natural Science Foundation Program, No. KJT13066; the Bagui Scholars Foundation Program of Guangxi; the Special-term Experts Foundation Program of Guangxi; and the Project of Guangxi Young Teacher Fundamental Ability Promotion, No. 2017KY0298.
Institutional review board statement: The study was approved by the institutional review board of our hospital.
Institutional animal care and use committee statement: We did not use animals in our present study.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to 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/
Corresponding author: Xin Deng, MD, PhD, Professor, School of Basic Science, Guangxi University of Chinese Medicine, 13 Xianhu Avenue, Nanning 530200, Guangxi Zhuang Autonomous Region, China. 260446391@qq.com
Telephone: +86-771-2239080 Fax: +86-771-2239080
Received: December 5, 2018
Peer-review started: December 6, 2018
First decision: January 11, 2019
Revised: January 24, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: March 7, 2019
Processing time: 93 Days and 2.3 Hours
Abstract
BACKGROUND

Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells (HSCs). Since the molecular mechanism of taurine-mediated antifibrotic activity has not been fully unveiled and is little studied, it is imperative to use “omics” methods to systematically investigate the molecular mechanism by which taurine inhibits liver fibrosis.

AIM

To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis.

METHODS

We used microarrays, bioinformatics, protein-protein interaction (PPI) network, and sub-modules to investigate taurine-induced changes in gene expression in human HSCs (LX-2). Subsequently, all of the differentially expressed genes (DEGs) were subjected to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Furthermore, the interactions of DEGs were explored in a human PPI network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software.

RESULTS

A total of 635 DEGs were identified in taurine-treated HSCs when compared with the controls. Of these, 304 genes were statistically significantly up-regulated, and 331 down-regulated. Most of these DEGs were mainly located on the membrane and extracellular region, and are involved in the biological processes of signal transduction, cell proliferation, positive regulation of extracellular regulated protein kinases 1 (ERK1) and ERK2 cascade, extrinsic apoptotic signaling pathway and so on. Fifteen significantly enriched pathways with DEGs were identified, including mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferators-activated receptor signaling pathway, estrogen signaling pathway, Th1 and Th2 cell differentiation, cyclic adenosine monophosphate signaling pathway and so on. By integrating the transcriptomics and human PPI data, nine critical genes, including MMP2, MMP9, MMP21, TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF, were identified in the PPI network analysis.

CONCLUSION

Taurine promotes the apoptosis of HSCs via up-regulating TGFB1 and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. These findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.

Keywords: Taurine, Hepatic stellate cells, Differentially expressed genes, Liver fibrogenesis, Transcriptomic, Protein-protein interaction network

Core tip: We report our results derived from integrating transcriptomic and protein-protein interaction data by methods of microarrays, bioinformatics, protein-protein interaction network, and sub-modules, which allowed us to identify the key targets genes involved in taurine-promoted hepatic stellate cell (HSC) apoptosis. This study demonstrates for the first time that taurine promotes the apoptosis of HSCs via up-regulating TGFB1 and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. MMP2, MMP9, MMP21, TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF may be the important targets of taurine in HSCs.