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Evodiamine attenuates TGF-β1-induced fibroblast activation and endothelial to mesenchymal transition

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Abstract

The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time. The EndMT response in the HUVECs was evaluated as well as the capacity of the transitioned endothelial cells migrating to surrounding tissue. As a result, Evodiamine-blunted TGF-β1 induced activation of cardiac fibroblast into myofibroblast as assessed by the decreased expressions of α-SMA. Furthermore, evodiamine reduced the increased protein expression of fibrosis markers in neonatal and adult rat cardiac fibroblasts induced by TGF-β1. HUVECs stimulated with TGF-β1 exhibited lower expression levels of CD31, CD34, and higher levels of α-SMA, vimentin than the control cells. This phenotype was eliminated in the HUVECs treated with both 5 and 10 μM evodiamine. Evodiamine significantly reduced the increase in migration ability that occurred in response to TGF-β1 in HUVECs. In addition, the activation of Smad2, Smad3, ERK1/2, and Akt, and the nuclear translocation of Smad4 in both cardiac fibroblasts and HUVEC were blocked by evodiamine treatment. Thus, evodiamine could prevent cardiac fibroblasts from activation into myofibroblast and protect HUVEC against EndMT. These effects may be mediated by inhibition of the TGFβ pathway in both cardiac fibroblasts and HUVECs.

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Author contributions

Qing–Qing Wu and Qi-Zhu Tang contributed to conception and designed experiments; Qing–Qing Wu and Yang Xiao, Xiao-Han Jiang and Yuan Yuan carried out experiments; Zheng Yang and Zhou-Yan Bian analyzed experimental results and revised the manuscript. Qing–Qing Wu and Wei Chang wrote and revised the manuscript.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81470516, 81530012, and 81470402), Hubei Province’s Outstanding Medical Academic Leader program.

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People’s Republic of China

    Qing-Qing Wu, Yang Xiao, Xiao-Han Jiang, Yuan Yuan, Zheng Yang, Wei Chang, Zhou-Yan Bian & Qi-Zhu Tang

  2. Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People’s Republic of China

    Qing-Qing Wu, Yang Xiao, Xiao-Han Jiang, Yuan Yuan, Zheng Yang, Wei Chang, Zhou-Yan Bian & Qi-Zhu Tang

  3. Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China

    Qing-Qing Wu, Yang Xiao, Xiao-Han Jiang, Yuan Yuan, Zheng Yang, Wei Chang, Zhou-Yan Bian & Qi-Zhu Tang

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  1. Qing-Qing Wu
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  2. Yang Xiao
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Correspondence to Qi-Zhu Tang.

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Wu, QQ., Xiao, Y., Jiang, XH. et al. Evodiamine attenuates TGF-β1-induced fibroblast activation and endothelial to mesenchymal transition. Mol Cell Biochem 430, 81–90 (2017). https://doi.org/10.1007/s11010-017-2956-6

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  • DOI: https://doi.org/10.1007/s11010-017-2956-6

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