Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China.
College of Medical, Guangxi University, Nanning 530004, Guangxi Zhuang Autonomous Region, China.
World J Gastroenterol. 2019 Mar 7;25(9):1067-1079. doi: 10.3748/wjg.v25.i9.1067.
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.
To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis.
We used microarrays, bioinformatics, protein-protein interaction (PPI) network, and sub-modules to investigate taurine-induced changes in gene expression in human HSCs (). 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.
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 , , , , , , , , and , were identified in the PPI network analysis.
Taurine promotes the apoptosis of HSCs up-regulating 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.
研究表明，牛磺酸的抗纤维化机制可能涉及抑制肝星状细胞（HSCs）的激活和增殖。由于牛磺酸介导的抗纤维化活性的分子机制尚未完全揭示，并且研究较少，因此必须使用“组学”方法系统地研究牛磺酸抑制肝纤维化的分子机制。
建立一个包含转录组和蛋白质-蛋白质相互作用（PPI）网络的网络，以阐明牛磺酸诱导的 HSC 凋亡的分子机制。
我们使用微阵列、生物信息学、蛋白质-蛋白质相互作用（PPI）网络和子模块来研究牛磺酸诱导的人 HSCs（）中基因表达的变化。随后，对所有差异表达基因（DEGs）进行基因本体功能和京都基因与基因组百科全书通路富集分析。此外，在人类 PPI 网络中探索 DEGs 的相互作用，并使用 Cytoscape 软件分析 DEGs 相互作用网络的子模块。
与对照组相比，牛磺酸处理的 HSCs 中共鉴定出 635 个 DEGs。其中，304 个基因显著上调，331 个基因下调。这些 DEGs 大多数主要位于膜和细胞外区，参与信号转导、细胞增殖、细胞外调节蛋白激酶 1（ERK1）和 ERK2 级联的正调控、外在凋亡信号通路等生物学过程。鉴定出 15 个具有 DEGs 的显著富集途径，包括丝裂原活化蛋白激酶（MAPK）信号通路、过氧化物酶体增殖物激活受体信号通路、雌激素信号通路、Th1 和 Th2 细胞分化、环磷酸腺苷信号通路等。通过整合转录组学和人类 PPI 数据，在 PPI 网络分析中鉴定出 9 个关键基因，包括、、、、、、、和。
牛磺酸通过上调和激活 p38 MAPK-JNK-Caspase9/8/3 通路促进 HSCs 凋亡。这些发现增强了对牛磺酸诱导的 HSC 凋亡分子机制的理解，为肝脏疾病治疗提供了参考。
