May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
VEGF-B Inhibits the Expression of Apoptotic/Cell Death-Related Genes in Multiple Types of Cells
Author Affiliations & Notes
  • P. Arjunan
    NEI/NIH, Bethesda, Maryland
  • Y. Li
    NEI/NIH, Bethesda, Maryland
  • F. Zhang
    NEI/NIH, Bethesda, Maryland
  • Z. Tang
    NEI/NIH, Bethesda, Maryland
  • C.-H. Heldin
    Ludwig Institute for Cancer Research, Uppsala University., BMC, SE-75124 Uppsala, Sweden
  • X. Li
    NEI/NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  P. Arjunan, None; Y. Li, None; F. Zhang, None; Z. Tang, None; C. Heldin, None; X. Li, None.
  • Footnotes
    Support  The Intramural Research Program of the NIH,National Institute on Aging, and the National Eye Institute.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4948. doi:
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      P. Arjunan, Y. Li, F. Zhang, Z. Tang, C.-H. Heldin, X. Li; VEGF-B Inhibits the Expression of Apoptotic/Cell Death-Related Genes in Multiple Types of Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4948.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To determine the anti-apoptotic effect of VEGF-B, we performed the genome-wide gene expression profiling and identified the VEGF-B regulated genes.

Methods: : The mouse primary aortic smooth muscles cells expressing VEGFR-1 were treated with human recombinant VEGF-B167 protein under hypoxia (1% oxygen), a condition in which VEGFR-1 is up-regulated in these cells. Results revealed that VEGF-B treatment significantly down-regulated the expression of about six hundred genes by more than two-fold. Among the significant genes consisted in the apoptosis/cell death-related pathways, those ranked among the top 3 in terms of significance in down-regulation - Bmf (~10-fold), TrP53inp1 (~ 8-fold), and DCN (~ 7-fold)- were found to be critically involved in apoptosis.

Results: : For verification of the microarray data, five different cell lines - RGC5 (rat retinal ganglion cell-derived), TR-rPCT (immortalized rat retinal pericyte), TR-MUL (immortalized rat retinal, Müller), TR-iBRB (immortalized rat retinal endothelial), and the mouse primary aortic smooth muscle cells (mSMC) - were treated with VEGF-B167 (100 ng/ml) for six hours in either normoxic or hypoxic (1% oxygen) conditions, and the expression of the apoptotic/cell death-related genes investigated by real-time PCR. Consistent with the microarray data, the expression of many apoptotic/cell death-related genes were found to be significantly inhibited by VEGF-B. Among them, the expression of most of the BH3-only protein genes (Bmf, Hrk, Puma, Noxa (Pmaip1), Bid, Bad, Bik) was inhibited by VEGF-B in all types of cells examined. The BH3-only protein genes are therefore the major target genes suppressed by VEGF-B. It also inhibited the expression of p53, the caspases (Casp2, Casp8, Casp9, Casp12), and other apoptotic/cell death-related genes (Bak, Bax, Bcl2l11, TNF-α, Dcn, Olr1, etc).

Conclusions: : In conclusion, the VEGF-B inhibited the expression of the BH3-only protein and other apoptotic/cell death-related genes, indicating a general anti-apoptotic effect of VEGF-B in different cell types, and thus may provide a new therapeutic intervention for retinal degenerative process.

Keywords: apoptosis/cell death • gene microarray • retinal degenerations: cell biology 
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