Transcriptome Analysis of the Anti-TGFβ Effect of Schisandra chinensis Fruit Extract and Schisandrin B in A7r5 Vascular Smooth Muscle Cells.
Transcriptome Analysis of the Anti-TGFβ Effect of Schisandra chinensis Fruit Extract and Schisandrin B in A7r5 Vascular Smooth Muscle Cells.
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DOI：
10.3390/life11020163
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发表时间：
2021-02-20
期刊：
影响因子：
--
通讯作者：
Park EJ
中科院分区：
文献类型：
--
作者：
Lee S;Chun JN;Lee HJ;Park HH;So I;Jeon JH;Park EJ
五味子果实提取物（SCE）是治疗血管疾病的传统药物。然而，SCE和五味子醇甲B（SchB）如何影响血管平滑肌细胞（VSMC）转化生长因子β（TGFβ）信号通路的转录输出，这是形成纤维化反应的关键因素，目前尚不清楚。在这项研究中，为了评估SCE和SchB对TGFβ诱导的转录输出的药理作用，我们在A7 r5 VSMCs中进行了DNA微阵列实验。我们发现TGFβ诱导了基因表达谱的显著变化，SCE和SchB可显著逆转这些变化。具有Hallmark签名的基因集富集分析（GSEA）表明SCE或SchB抑制一系列纤维化相关的生物过程，包括炎症、细胞增殖和迁移。利用我们的VSMC特异性转录相互作用组网络，主调节因子分析鉴定了调节SCE和SchB有效基因表达的关键转录因子（即，TGFβ-反应基因，其表达被SCE和SchB逆转）。我们的研究结果为理解SCE和SchB在转录组水平上的药理作用提供了新的视角和见解，并将支持进一步的研究，以开发多靶点治疗血管纤维化的策略。
Schisandra chinensis fruit extract (SCE) has been used as a traditional medicine for treating vascular diseases. However, little is known about how SCE and schisandrin B (SchB) affect transcriptional output-a crucial factor for shaping the fibrotic responses of the transforming growth factor β (TGFβ) signaling pathways in in vascular smooth muscle cells (VSMC). In this study, to assess the pharmacological effect of SCE and SchB on TGFβ-induced transcriptional output, we performed DNA microarray experiments in A7r5 VSMCs. We found that TGFβ induced distinctive changes in the gene expression profile and that these changes were considerably reversed by SCE and SchB. Gene Set Enrichment Analysis (GSEA) with Hallmark signature suggested that SCE or SchB inhibits a range of fibrosis-associated biological processes, including inflammation, cell proliferation and migration. With our VSMC-specific transcriptional interactome network, master regulator analysis identified crucial transcription factors that regulate the expression of SCE- and SchB-effective genes (i.e., TGFβ-reactive genes whose expression are reversed by SCE and SchB). Our results provide novel perspective and insight into understanding the pharmacological action of SCE and SchB at the transcriptome level and will support further investigations to develop multitargeted strategies for the treatment of vascular fibrosis.
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DOI：
10.1016/j.bbrc.2012.05.010
发表时间：
2012-06-08
影响因子：
3.1
作者：
Kim, Su-Hwa;Lee, Sanghoon;Jeon, Ju-Hong
通讯作者：
Jeon, Ju-Hong
DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Biernacka A;Dobaczewski M;Frangogiannis NG
通讯作者：
Frangogiannis NG
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影响因子：
1.1
作者：
Li, Jia-Qi;Gong, Jing-Yu;Wang, Jian-She
通讯作者：
Wang, Jian-She
影响因子：
4
作者：
Lee, Sanghoon;Park, Yu Rang;Kim, Su-Hwa;Park, Eun-Jung;Kang, Min Ji;So, Insuk;Chun, Jung Nyeo;Jeon, Ju-Hong
通讯作者：
Jeon, Ju-Hong
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y