Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway.
Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway.
复制标题
DOI：
10.1139/cjpp-2016-0676
复制
发表时间：
2018
影响因子：
2.1
通讯作者：
Weirong Wang;T. Jing;Xiaofeng Yang;Yanhao He;Bo Wang;Yunfang Xiao;Chenxu Shang;Jiye Zhang;R. Lin
中科院分区：
文献类型：
--
作者：
Weirong Wang;T. Jing;Xiaofeng Yang;Yanhao He;Bo Wang;Yunfang Xiao;Chenxu Shang;Jiye Zhang;R. Lin
羟基酪醇（HT）是橄榄油中的一种酚类化合物，在心血管疾病中发挥抗炎作用。近年来的研究发现自噬是疾病治疗的一个靶点。然而，HT对血管外膜成纤维细胞（VAF）自噬的影响仍然未知。因此，在本研究中，我们的目的是确定HT对细胞自噬和相关信号通路的影响，以及HT是否通过自噬调节VAF的炎症反应。结果表明，HT通过增加肿瘤坏死因子-α（TNF-α）刺激的VAFs中LC 3和Beclin 1表达的转化以及自噬流量，促进细胞自噬。与TNF-α组相比，HT还上调了去乙酰化酶sirtuin 1（SIRT 1）蛋白和mRNA的表达。分子对接研究表明HT与SIRT 1之间具有良好的相容性，提示HT可能通过SIRT 1发挥作用。进一步的研究发现，HT通过SIRT 1介导的Akt/mTOR抑制VAF中的自噬来调节。此外，HT还通过SIRT 1抑制TNF-α诱导的VAF炎症反应。此外，研究表明HT通过自噬抑制VAF的炎症反应。这些结果表明，HT通过SIRT 1介导的Akt/mTOR抑制来调节VAFs的自噬，从而抑制VAFs的炎症反应。
Hydroxytyrosol (HT), a phenolic compound in olive oil, exerts an anti-inflammatory effect in cardiovascular diseases. Recent studies found that autophagy was a therapeutic target of diseases. However, the effect of HT on autophagy in vascular adventitial fibroblasts (VAFs) remains unknown. Thus, in this study, we aimed to determine the effect of HT on cell autophagy and related signaling pathway and whether HT regulates the inflammatory response through autophagy in VAFs. Our results showed that HT promoted cell autophagy by increasing the conversion of LC3 and Beclin1 expression and the autophagic flux in VAFs stimulated with tumor necrosis factor-α (TNF-α). HT also upregulated the expression of the deacetylase sirtuin 1 (SIRT1) protein and mRNA compared with the TNF-α group. The molecular docking studies showed the good compatibility between HT and SIRT1, indicating that HT might act through SIRT1. Further study found that HT regulated autophagy through SIRT1-mediated Akt/mTOR suppression in VAFs. In addition, HT inhibited TNF-α-induced inflammatory response in VAFs through SIRT1. Furthermore, the study showed that HT inhibited the inflammatory response of VAFs through autophagy. These findings indicate that HT regulates the autophagy of VAFs through SIRT1-mediated Akt/mTOR suppression and then inhibits the inflammatory response of VAFs.