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首页> 外文期刊>Biomolecules & therapeutics >Aspirin-Triggered Resolvin D1 Inhibits TGF-beta 1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress
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Aspirin-Triggered Resolvin D1 Inhibits TGF-beta 1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress

机译:阿司匹林引发的Resolvin D1通过增加Smad7的表达抑制TGF-β1诱导的EndMT,并且与氧化应激密切相关

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摘要

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 beta 1 (TGF-beta 1) 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-beta 1-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-beta 1 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 kappa 3 kinase 16 (IKK 16), which is known to inhibit the NF-kappa B pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-beta 1-induced EndMT, but it had no effect on TGF-beta 1-induced EndMT alone. Smad7, which is a key regulator of TGF-beta/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-beta 1-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.
机译:已知内皮-间质转化(EndMT)参与了血管内皮细胞向间充质细胞的转化。已确认EndMT会在各种病理状况下发生。转化生长因子beta 1(TGF-beta 1)是血管内皮细胞向间质转化(EMT)的有效刺激剂。已知阿司匹林触发的resolvin D1(ATRvD1)与炎症的消退有关,但尚不清楚它是否对TGF-β1诱导的EndMT有影响。因此,我们研究了AT-RvD1对人脐静脉血管内皮细胞系(HUVECs)EndMT的影响。使用TGF-beta 1进行治疗可降低Nrf2的表达并提高F-肌动蛋白的水平,这与细胞旁通透性有关。 HUVEC细胞中内皮标志物VE-cadherin的表达降低,间质标志物波形蛋白的表达增强。 AT-RvD1恢复了Nrf2和波形蛋白的表达,并增强了VE-钙粘蛋白的表达。 AT-RvD1也确实影响了HUVEC细胞的迁移。已知抑制NF-κB通路的抑制性Kappa 3激酶16(IKK 16)具有增加Nrf2表达的能力,并且与AT-RvD1对TGF-β1诱导的EndMT的抑制作用有关。 ,但仅对TGF-β1诱导的EndMT没有影响。 Smad7是通过负反馈回路对TGF-beta / Smads信号进行调节的关键调节剂,在治疗AT-RvD1后,其表达显着增加。这些结果表明,AT-RvD1通过增加Smad7的表达抑制TGF-β1诱导的EndMT的可能性,并且与氧化应激密切相关。

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