Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Aspirin-Triggered Resolvin D1 Inhibits TGF-β1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress

  • Shu, Yusheng (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital) ;
  • Liu, Yu (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital) ;
  • Li, Xinxin (Department of Cardiothoracic Surgery, Subei People's Hospital) ;
  • Cao, Ling (Department of Endocrinology, Clinical Medicine College of Yangzhou University, Subei People's Hospital) ;
  • Yuan, Xiaolong (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital) ;
  • Li, Wenhui (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital) ;
  • Cao, Qianqian (Department of Cardiothoracic Surgery, Subei People's Hospital)
  • Received : 2015.07.01
  • Accepted : 2015.11.12
  • Published : 2016.03.01
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Abstract

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 (AT-RvD1) 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 ${\kappa}B$ 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.

Keywords

References

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