Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin

  • Authors:
    • K. Riedel
    • E. Koellensperger
    • H. Ryssel
    • F. Riedel
    • U. R. Goessler
    • G. Germann
    • T. Kremer
  • View Affiliations

  • Published online on: October 1, 2008     https://doi.org/10.3892/ijmm_00000045
  • Pages: 473-480
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Abstract

The transforming growth factor-β (TGF-β) has been identified as an important component of wound healing. Recent developments in molecular therapy offer good prospects for the modulation of wound healing, specifically those targeting TGF-β. The aim of this study was to analyze the effect of TGF-β targeting on the expression of angiogenic vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and in vitro angiogenic activity in fibroblasts isolated from radiation-induced chronic dermal wounds. The expression of angiogenic VEGF in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-β targeting using antisense oligonucleotides on the expression of VEGF in isolated fibroblasts was analyzed by ELISA and multiplex RT-PCR. Human endothelial cells (ECs) were grown in conditioned medium produced from the treated fibroblasts. EC migration was measured using a modified Boyden chamber; EC tube formation was analyzed under a light microscope. Immunohistochemical investigation and microarray analysis demonstrated a decreased expression of VEGF protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-β oligonucleotide treatment significantly up-regulated VEGF secretion in vitro. Addition of conditioned medium from TGF-β antisense-treated fibroblasts resulted in an increase in EC cell migration and tube formation. In conclusion, our results demonstrate that TGF-β antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in radiation-induced dermal wounds.

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October 2008
Volume 22 Issue 4

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

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Spandidos Publications style
Riedel K, Koellensperger E, Ryssel H, Riedel F, Goessler UR, Germann G and Kremer T: Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin. Int J Mol Med 22: 473-480, 2008.
APA
Riedel, K., Koellensperger, E., Ryssel, H., Riedel, F., Goessler, U.R., Germann, G., & Kremer, T. (2008). Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin. International Journal of Molecular Medicine, 22, 473-480. https://doi.org/10.3892/ijmm_00000045
MLA
Riedel, K., Koellensperger, E., Ryssel, H., Riedel, F., Goessler, U. R., Germann, G., Kremer, T."Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin". International Journal of Molecular Medicine 22.4 (2008): 473-480.
Chicago
Riedel, K., Koellensperger, E., Ryssel, H., Riedel, F., Goessler, U. R., Germann, G., Kremer, T."Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin". International Journal of Molecular Medicine 22, no. 4 (2008): 473-480. https://doi.org/10.3892/ijmm_00000045