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Resveratrol Ameliorates Systemic Sclerosis via Suppression of Fibrosis and Inflammation Through Activation of SIRT1/mTOR Signaling
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-12-02 , DOI: 10.2147/dddt.s281209 Qicen Yao 1 , Qingchao Wu 2 , Xiayu Xu 1 , Yixi Xing 1 , Jin Liang 1 , Qianqi Lin 1 , Meiqiong Huang 1 , Yiling Chen 1 , Bo Lin 3 , Weifei Chen 1
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-12-02 , DOI: 10.2147/dddt.s281209 Qicen Yao 1 , Qingchao Wu 2 , Xiayu Xu 1 , Yixi Xing 1 , Jin Liang 1 , Qianqi Lin 1 , Meiqiong Huang 1 , Yiling Chen 1 , Bo Lin 3 , Weifei Chen 1
Affiliation
Purpose: Resveratrol (Res) is a natural polyphenolic compound found in several plants and reported as a promising biological molecule with effective anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified the key cellular signaling pathways involved in the Res regulatory process on SSc.
Methods: Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines.
Results: Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation.
Conclusion: These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.
Keywords: resveratrol, systemic sclerosis, SIRT1, mTOR, signaling
中文翻译：
白藜芦醇通过激活 SIRT1/mTOR 信号传导抑制纤维化和炎症来改善系统性硬化症
目的：白藜芦醇 (Res) 是一种在多种植物中发现的天然多酚化合物，被报道为具有有效抗纤维化和抗炎活性的有前途的生物分子。然而，Res 对系统性硬化症 (SSc) 的潜在机制仍不清楚。在这项研究中，我们确定了参与 SSc 的 Res 调节过程的关键细胞信号通路。
方法：使用 STITCH 数据库构建 Res 靶向基因相互作用网络，然后确定了涉及 SSc 和 Res 靶向基因的共享京都基因和基因组百科全书 (KEGG) 途径。GOplot 可视化了前 5 个富集的 KEGG 通路。与 Res 靶向基因相关的 KEGG 通路由 Pathway Builder Tool 2.0 建立。定量实时 PCR (qRT-PCR) 用于评估 sirtuin 1 (SIRT1)、哺乳动物雷帕霉素靶向 (mTOR) 和细胞因子的表达。
结果：Res 靶向基因的富集分析显示 79 条相关通路，其中 27 条也参与 SSc。特别是，发现 SIRT1/mTOR 信号是关键的调节途径之一。体外结果表明 SIRT1 介导的 mTOR 降解改善了博来霉素 (BLM) 诱导的纤维化和炎症。Res 能够提高成纤维细胞中的 SIRT1 水平，并部分逆转 mTOR 依赖性纤维化和炎症的诱导。
结论：这些结果表明，Res是治疗SSc可行且有效的选择，mTOR的治疗靶点可能是治疗SSc的潜在替代方案。
关键词：白藜芦醇，系统性硬化症，SIRT1，mTOR，信号传导
更新日期：2020-12-02
Methods: Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines.
Results: Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation.
Conclusion: These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.
Keywords: resveratrol, systemic sclerosis, SIRT1, mTOR, signaling
中文翻译：
白藜芦醇通过激活 SIRT1/mTOR 信号传导抑制纤维化和炎症来改善系统性硬化症
目的：白藜芦醇 (Res) 是一种在多种植物中发现的天然多酚化合物，被报道为具有有效抗纤维化和抗炎活性的有前途的生物分子。然而，Res 对系统性硬化症 (SSc) 的潜在机制仍不清楚。在这项研究中，我们确定了参与 SSc 的 Res 调节过程的关键细胞信号通路。
方法：使用 STITCH 数据库构建 Res 靶向基因相互作用网络，然后确定了涉及 SSc 和 Res 靶向基因的共享京都基因和基因组百科全书 (KEGG) 途径。GOplot 可视化了前 5 个富集的 KEGG 通路。与 Res 靶向基因相关的 KEGG 通路由 Pathway Builder Tool 2.0 建立。定量实时 PCR (qRT-PCR) 用于评估 sirtuin 1 (SIRT1)、哺乳动物雷帕霉素靶向 (mTOR) 和细胞因子的表达。
结果：Res 靶向基因的富集分析显示 79 条相关通路，其中 27 条也参与 SSc。特别是，发现 SIRT1/mTOR 信号是关键的调节途径之一。体外结果表明 SIRT1 介导的 mTOR 降解改善了博来霉素 (BLM) 诱导的纤维化和炎症。Res 能够提高成纤维细胞中的 SIRT1 水平，并部分逆转 mTOR 依赖性纤维化和炎症的诱导。
结论：这些结果表明，Res是治疗SSc可行且有效的选择，mTOR的治疗靶点可能是治疗SSc的潜在替代方案。
关键词：白藜芦醇，系统性硬化症，SIRT1，mTOR，信号传导
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