Published online Mar 7, 2019. doi: 10.3748/wjg.v25.i9.1067
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
Taurine is a beta amino acid with a simple structure and mostly appears in the free state in organism, and it plays a protective role against several forms of hepatic damage, including hepatic fibrosis. However, the molecular mechanism of taurine remains unclear, and therefore, it is difficult to use taurine for precision therapies in liver diseases.
The main topics of this study included investigating taurine-induced changes in gene expression in human HSCs, subjecting all of the differential expressed genes to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis, exploring the interactions of differentially expressed genes (DEGs) in a human protein-protein interaction (PPI) network, and clarifying the mechanism of taurine on human hepatic stellate cells (HSCs). The findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.
The present study aimed to establish a network including transcriptomic and protein-protein interaction data, and to elucidate the molecular mechanism of taurine-induced HSC apoptosis.
Raw microarray data were obtained as “.IDAT” and “.SDF” format using Genome Studio software (Illumina, San Diego, CA, United States), and then imported into the R environment for further processing. Subsequently, quantile normalization was carried out in R using the lumi package with Bioconductor open source software (http://www.bioconductor.org/). Significance was calculated using a t-test without multiple testing correction, selecting all transcripts with a minimum change in expression level of 1.5-fold together with a P-value less than 0.05. An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the PPI network was constructed using Cytoscape software. Furthermore, the MCODE plug-in of Cytoscape was used to conduct a sub-module analysis.
It was found that nine critical genes, including MMP2, MMP9, MMP21, TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF, were screened in the PPI network analysis.
The present study showed that VEGFB, EGF, BDNF, TGFB1, FIGF, TIMP3, FGB, EGFR, F7, MMP9, MMRN1, and TCOF1 play key roles in the action mechanism of taurine, and these DEGs are mainly involved in positive regulation of protein kinase B signaling, ERK1 and ERK2 cascade, MAP kinase activity, MAPK cascade, cell migration, and cell proliferation.
This study preliminarily explored the molecular mechanism of taurine on HSCs. Future studies should focus on the following aspects. First, the present study had no validation data and the findings could not be generalized to other conditions. As a result, future research should conduct the validate experiments, including the differentially expressed genes and the p38 MAPK-JNK-Caspase9/8/3 pathway by using blockers via the method of PCR and Western blot. Second, the characters of active and quiescent HSCs are different and the two subtypes should be studied separately in the future.