FHL1 and Smad4 synergistically inhibit vascular endothelial growth factor expression

  • Authors:
    • Zhichao Zhou
    • Juming Lu
    • Jingtao Dou
    • Zhaohui Lv
    • Xi Qin
    • Jing Lin
  • View Affiliations

  • Published online on: November 26, 2012     https://doi.org/10.3892/mmr.2012.1202
  • Pages: 649-653
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Abstract

Vascular endothelial growth factor (VEGF) plays an important role in many disease states, including ischemia, chronic and acute inflammation, and pathologies associated with angiogenesis such as tumors and wounds. A number of factors regulate VEGF promoter activity and VEGF expression such as four and a half LIM domains 1 (FHL1) and Smad4. FHL1 belongs to a family of LIM-only proteins that regulate gene transcription, cell proliferation, differentiation and apoptosis. Smad4 is a tumor suppressor gene, initially identified as deleted in pancreatic carcinoma locus 4 (DPC4). The aim of this study was to determine whether FHL1 and Smad4 inhibited VEGF signaling. HepG2 cells were transfected with the VEGF-Luc reporter, Smad4 and FHL1 or Smad4 and FHL1 siRNA. Results showed that the overexpression of FHL1 and Smad4 synergistically inhibited the promoter activity, mRNA expression and secretion of VEGF, whereas knockdown of endogenous Smad4 and FHL1 had opposite effects. Moreover, the reduction of endogenous Smad4 eliminated FHL1-mediated inhibition of the VEGF promoter activity. In conclusion, a cooperative regulation of VEGF signaling by FHL1 and Smad4 was evidenced, which may provide a novel regulation mechanism underlying cancer development and progression.
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February 2013
Volume 7 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhou Z, Lu J, Dou J, Lv Z, Qin X and Lin J: FHL1 and Smad4 synergistically inhibit vascular endothelial growth factor expression. Mol Med Rep 7: 649-653, 2013
APA
Zhou, Z., Lu, J., Dou, J., Lv, Z., Qin, X., & Lin, J. (2013). FHL1 and Smad4 synergistically inhibit vascular endothelial growth factor expression. Molecular Medicine Reports, 7, 649-653. https://doi.org/10.3892/mmr.2012.1202
MLA
Zhou, Z., Lu, J., Dou, J., Lv, Z., Qin, X., Lin, J."FHL1 and Smad4 synergistically inhibit vascular endothelial growth factor expression". Molecular Medicine Reports 7.2 (2013): 649-653.
Chicago
Zhou, Z., Lu, J., Dou, J., Lv, Z., Qin, X., Lin, J."FHL1 and Smad4 synergistically inhibit vascular endothelial growth factor expression". Molecular Medicine Reports 7, no. 2 (2013): 649-653. https://doi.org/10.3892/mmr.2012.1202