Gene therapy with an E2F transcription factor decoy inhibits cell cycle progression in rat anti-Thy 1 glomerulonephritis

  • Authors:
    • Naruya Tomita
    • John Y.S. Kim
    • Gary H. Gibbons
    • Lunan Zhang
    • Yasufumi Kaneda
    • Rolf A.K. Stahl
    • Malcom Ogborn
    • Benoit Venderville
    • Ryuichi Morishita
    • Dana Baran
    • Victro J. Dzau
  • View Affiliations

  • Published online on: May 1, 2004     https://doi.org/10.3892/ijmm.13.5.629
  • Pages: 629-636
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Abstract

Mesangial cell (MC) proliferation is a central feature of many glomerular diseases. Various growth factors and cytokines are known to trigger MC proliferation both in vitro and in vivo. Regardless of the initial stimulus, proliferation is ultimately dependent upon the coordinated activation of cell cycle regulatory genes whose transcription is tightly controlled in mammalian cells. The transcription factor E2F plays an important role in the transactivation of the cell cycle regulatory genes proliferating-cell nuclear antigen (PCNA) and cdk2 kinase. To test whether or not E2F inhibition would blunt glomerular cell cycling in vivo, we treated rats with anti-Thy 1 antibody to induce glomerular injury, and that infused hemagglutinating virus of Japan (HVJ)-liposomes containing synthetic double stranded oligonucleotides (ODN) with high affinity for E2F (E2F decoy) directly into one kidney. First, we confirmed that with HVJ-liposome method fluorescence isothiocynate (FITC)-labeled ODN could be efficiently introduced into rat glomerular cells via renal artery. E2F decoy ODN treatment specifically inhibited mRNA expression of PCNA and cdk2 kinase in kidneys injured with anti-Thy 1 antibody as assessed by RT-PCR. This was associated with a significant decrease in number of glomerular cells in S phase as assessed by 5'-bromo-2'-deoxy-uridine labeling method, and attenuation of glomerular injury assessed histologically. The evidence suggests that intra-renal delivery of E2F decoy ODN by HVJ-liposome method prevents the induction of cell cycle regulatory gene expression and MC proliferation. These data also demonstrate the feasibility and the potential benefit of in vivo gene therapy as a novel strategy in the treatment of glomerular diseases.

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May 2004
Volume 13 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tomita N, Kim JY, Gibbons GH, Zhang L, Kaneda Y, Stahl RA, Ogborn M, Venderville B, Morishita R, Baran D, Baran D, et al: Gene therapy with an E2F transcription factor decoy inhibits cell cycle progression in rat anti-Thy 1 glomerulonephritis. Int J Mol Med 13: 629-636, 2004
APA
Tomita, N., Kim, J.Y., Gibbons, G.H., Zhang, L., Kaneda, Y., Stahl, R.A. ... Dzau, V.J. (2004). Gene therapy with an E2F transcription factor decoy inhibits cell cycle progression in rat anti-Thy 1 glomerulonephritis. International Journal of Molecular Medicine, 13, 629-636. https://doi.org/10.3892/ijmm.13.5.629
MLA
Tomita, N., Kim, J. Y., Gibbons, G. H., Zhang, L., Kaneda, Y., Stahl, R. A., Ogborn, M., Venderville, B., Morishita, R., Baran, D., Dzau, V. J."Gene therapy with an E2F transcription factor decoy inhibits cell cycle progression in rat anti-Thy 1 glomerulonephritis". International Journal of Molecular Medicine 13.5 (2004): 629-636.
Chicago
Tomita, N., Kim, J. Y., Gibbons, G. H., Zhang, L., Kaneda, Y., Stahl, R. A., Ogborn, M., Venderville, B., Morishita, R., Baran, D., Dzau, V. J."Gene therapy with an E2F transcription factor decoy inhibits cell cycle progression in rat anti-Thy 1 glomerulonephritis". International Journal of Molecular Medicine 13, no. 5 (2004): 629-636. https://doi.org/10.3892/ijmm.13.5.629