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Natural taurine promotes apoptosis of human hepatic stellate cells in proteomics analysis.

ABSTRACT: AIM:To study the differential expression of proteins between natural taurine treated hepatic stellate cells and controls, and investigate the underlying regulatory mechanism of natural taurine in inhibiting hepatic fibrosis. METHODS:A proteomic strategy combining two-dimensional gel electrophoresis and ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) was used to study the differential expression of proteins and Western blotting was used to validate the results. Gene ontology (GO) method was utilized to analyze the functional enrichment of differentially expressed proteins. Flow cytometry was performed to compare the apoptosis rate between taurine-treated and untreated hepatic stellate cells (HSCs). RESULTS:Nineteen differentially expressed proteins (11 up-regulated and 8 down-regulated) were identified by 2D/MS, and the expression profiles of GLO1 and ANXA1 were validated by Western blotting. GO analysis found that these differentially expressed proteins were enriched within biological processes such as "cellular apoptosis", "oxidation reaction" and "metabolic process" in clusters. Flow cytometric analysis showed that taurine-treated HSCs had a significantly increased apoptosis rate when compared with the control group. CONCLUSION:Natural taurine can promote HSC apoptosis so as to inhibit hepatic fibrosis.

SUBMITTER: Deng X

PROVIDER: S-EPMC2856835 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Natural taurine promotes apoptosis of human hepatic stellate cells in proteomics analysis.

Deng Xin X Liang Jian J Lin Zhi-Xiu ZX Wu Fa-Sheng FS Zhang Ya-Ping YP Zhang Zhi-Wei ZW

World journal of gastroenterology 20100401 15

<h4>Aim</h4>To study the differential expression of proteins between natural taurine treated hepatic stellate cells and controls, and investigate the underlying regulatory mechanism of natural taurine in inhibiting hepatic fibrosis.<h4>Methods</h4>A proteomic strategy combining two-dimensional gel electrophoresis and ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) was used to study the differential expression of proteins and Western blott ...[more]

PMID: 20397272

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Project description: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.

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Natural taurine promotes apoptosis of human hepatic stellate cells in proteomics analysis.

Publications

Natural taurine promotes apoptosis of human hepatic stellate cells in proteomics analysis.

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