ORIGINAL ARTICLE

Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis

Mizuho Yamada¹, Kazuyoshi Kuwano¹, Takashige Maeyama¹, Michihiro Yoshimi¹, Naoki Hamada¹, Jutaro Fukumoto¹, Kensuke Egashira², Kenichi Hiasa², Koichi Takayama¹ and Yoichi Nakanishi¹

¹ Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
² Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Correspondence to:
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

Background: Transforming growth factor-ß1 (TGF-ß1) 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-ß1 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-ß1 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-ß1 strategy may have clinical application in the treatment of lung injury and fibrosis.

Abbreviations: IPF, idiopathic pulmonary fibrosis; TGF, transforming growth factor; TGFR, transforming growth factor receptor

Keywords: in vivo electroporation; pulmonary fibrosis; transforming growth factor-ß1; apoptosis; gene therapy

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