Aspirin-Triggered Resolvin D1 Inhibits TGF-β1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress.
Aspirin-Triggered Resolvin D1 Inhibits TGF-β1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress.
复制标题
DOI：
10.4062/biomolther.2015.088
复制
发表时间：
2016-03-01
影响因子：
3.7
通讯作者：
Cao Q
中科院分区：
文献类型：
--
作者：
Shu Y;Liu Y;Li X;Cao L;Yuan X;Li W;Cao Q
内皮-间充质转化（EndMT）参与了血管内皮细胞向间充质细胞的转化。EndMT已被证实在各种病理条件下发生。转化生长因子β1（Transforming growth factor β 1，TGF-β1）是血管内皮细胞向间质细胞转化（vascular endothelial to mesenchymal transition，EMT）的强刺激因子。阿司匹林触发的消退素D1（ATRvD 1）参与炎症的消退，但其是否对TGF-β1诱导的EndMT有影响尚不清楚。因此，我们研究了AT-RvD 1对人脐静脉血管内皮细胞系（HUVECs）EndMT的影响。TGF-β1处理降低了Nrf 2的表达，提高了与细胞旁通透性相关的F-actin的水平。内皮细胞标志物VE-cadherin的表达降低，间充质细胞标志物vimentin的表达增强。AT-RvD 1可恢复Nrf 2和vimentin的表达，并增强VE-cadherin的表达。AT-RvD 1对HUVEC细胞的迁移也有影响。抑制性κB激酶16（IKK 16）可抑制NF-κB通路，增加Nrf 2的表达，并与AT-RvD 1对TGF-β1诱导的EndMT的抑制作用有关，但对单独TGF-β1诱导的EndMT无影响。Smad 7是TGF-β/Smads信号传导的负反馈环的关键调节因子，在AT-RvD 1处理后显著增加。这些结果提示AT-RvD 1可能通过增加Smad 7的表达来抑制TGF-β1诱导的EndMT，并与氧化应激密切相关。
The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor β1 (TGF-β1) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (ATRvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-β1-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-β1 reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory κB kinase 16 (IKK 16), which is known to inhibit the NF-κB pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-β1-induced EndMT, but it had no effect on TGF-β1-induced EndMT alone. Smad7, which is a key regulator of TGF-β/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-β1-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.