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ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-β1/ALK5/Smad2 pathway

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Abstract

ZNF580 is a novel C2H2 zinc-finger nuclear transcription factor with potential involvement in the transforming growth factor-β1 (TGF-β1) signal transduction pathway. Emerging evidence suggests that TGF-β1 can regulate endothelial nitric oxide synthase (eNOS) expression in endothelial cells. This study aimed to determine if ZNF580 mediated eNOS expression and participated in endothelial cell migration and proliferation via the TGF-β1/Smad2/ZNF580/eNOS signaling pathway. Overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of eNOS expression. TGF-β1 downregulated both ZNF580 and eNOS at the mRNA and protein levels in concentration- and time-dependent manners. ZNF580 and eNOS downregulation induced by TGF-β1 was blocked by the specific TGF-β1 type I receptor ALK5 inhibitor, SB431542. Overexpression of ZNF580 attenuated TGF-β1-induced inhibition of EAhy926 cell growth and mobility, and vice versa. These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-β1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells.

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Abbreviations

TGF-β:

Transforming growth factor-β

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

RNAi:

RNA interference

GFP:

Green fluorescent protein

eNOS:

Endothelial nitric oxide synthase

PCR:

Polymerase chain reaction

AS:

Atherosclerosis

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Acknowledgments

We are grateful to Dr. Thomas Michel (Brigham and Women’s Hospital, Boston, MA, USA) for the generous gifts of the plasmids pGL3-basic and human pGL3-eNOS-Luc. This project was supported by the National Natural Science Foundation of China Grants (No. 81170106, No. 81200223) and Science Foundation of Logistics University CPAF (No. WHB201207).

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No competing financial interests exist.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Logistics University of Chinese People’s Armed Police Force, Huizhihuan Road 1, Dongli District, Tianjin, 300309, China

    Yuyu Luo, Ying Zhao, Juan Zhao & Wencheng Zhang

  2. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury Institute of Cardiovascular Disease, Chenglin Road 220, Dongli District, Tianjin, 300162, China

    Yuyu Luo & Wencheng Zhang

  3. Department of Orthopaedics, Tianjin Third Central Hospital, Jintang Road 83, Hedong District, Tianjin, 300070, China

    Xiaodong Li

Authors
  1. Yuyu Luo
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  2. Ying Zhao
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  3. Xiaodong Li
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  4. Juan Zhao
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  5. Wencheng Zhang
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Corresponding author

Correspondence to Wencheng Zhang.

Additional information

Yuyu Luo and Ying Zhao have contributed equally to this work.

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Luo, Y., Zhao, Y., Li, X. et al. ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-β1/ALK5/Smad2 pathway. Mol Cell Biochem 393, 199–207 (2014). https://doi.org/10.1007/s11010-014-2061-z

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  • DOI: https://doi.org/10.1007/s11010-014-2061-z

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