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Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis
  1. Mizuho Yamada1,
  2. Kazuyoshi Kuwano1,
  3. Takashige Maeyama1,
  4. Michihiro Yoshimi1,
  5. Naoki Hamada1,
  6. Jutaro Fukumoto1,
  7. Kensuke Egashira2,
  8. Kenichi Hiasa2,
  9. Koichi Takayama1,
  10. Yoichi Nakanishi1
  1. 1Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  2. 2Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  1. Correspondence to:
 Dr Kazuyoshi Kuwano
 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; kkuwano{at}kokyu.med.kyushu-u.ac.jp

Abstract

Background: Transforming growth factor-β1 (TGF-β1) has the potential to induce acute inflammation and apoptosis in lung epithelial cells and plays a central role in subsequent fibrosis.

Aims: To examine a new anti-TGF-β1 therapy against lung injury and fibrosis, which comprises the transfection of soluble TGF type II receptor (sTGFRII) gene into skeletal muscles by in vivo electroporation.

Methods: Soluble TGFRII was detectable between 1 and 14 days in the serum and significantly increased between 3 and 10 days after gene transfer into muscles. Based on these findings, the sTGFRII gene was injected at 3 days before or 4 days after the bleomycin instillation in order to examine the significance of TGF-β1 on the early inflammatory phase (day 0 to day 7) or the fibrotic phase (day 7 to day 14) in this model.

Results: Transfection of sTGFRII gene at 3 days before or 4 days after bleomycin instillation significantly attenuated apoptosis, injury, and fibrosis at 7 or 14 days, respectively. This method does not require the use of viral vector or neutralising antibody, and it is therefore possible to avoid problems regarding the pathogenicity of the viral vector or immunocomplex.

Conclusions: This novel anti-TGF-β1 strategy may have clinical application in the treatment of lung injury and fibrosis.

  • IPF, idiopathic pulmonary fibrosis
  • TGF, transforming growth factor
  • TGFR, transforming growth factor receptor
  • in vivo electroporation
  • pulmonary fibrosis
  • transforming growth factor-β1
  • apoptosis
  • gene therapy

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Footnotes

  • Published Online First 3 October 2006

  • Funding: This work was supported by a Grant-in-Aid for Scientific Research (17590793) from the Ministry of Education, Science and Culture of Japan.

  • Competing interests: None declared.

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