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

Mizuho Yamada, Kazuyoshi Kuwano, Takashige Maeyama, Michihiro Yoshimi, Naoki Hamada, Jutaro Fukumoto, Kensuke Egashira, Kenichi Hiasa, Koichi Takayama, Yoichi Nakanishi

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)916-920
Number of pages5
JournalJournal of Clinical Pathology
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 1 2007

Fingerprint

Electroporation
Growth Factor Receptors
Lung Injury
Transforming Growth Factors
Fibrosis
Genes
Transfection
Viral Antibodies
Apoptosis
Bleomycin
Neutralizing Antibodies
Virulence
Skeletal Muscle
Epithelial Cells
Inflammation
Muscles
Lung
Wounds and Injuries
Serum
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis. / Yamada, Mizuho; Kuwano, Kazuyoshi; Maeyama, Takashige; Yoshimi, Michihiro; Hamada, Naoki; Fukumoto, Jutaro; Egashira, Kensuke; Hiasa, Kenichi; Takayama, Koichi; Nakanishi, Yoichi.

In: Journal of Clinical Pathology, Vol. 60, No. 8, 01.08.2007, p. 916-920.

Research output: Contribution to journalArticle

Yamada, Mizuho ; Kuwano, Kazuyoshi ; Maeyama, Takashige ; Yoshimi, Michihiro ; Hamada, Naoki ; Fukumoto, Jutaro ; Egashira, Kensuke ; Hiasa, Kenichi ; Takayama, Koichi ; Nakanishi, Yoichi. / Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis. In: Journal of Clinical Pathology. 2007 ; Vol. 60, No. 8. pp. 916-920.
@article{71c23a8aba02449ab464c9457953477b,
title = "Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis",
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.",
author = "Mizuho Yamada and Kazuyoshi Kuwano and Takashige Maeyama and Michihiro Yoshimi and Naoki Hamada and Jutaro Fukumoto and Kensuke Egashira and Kenichi Hiasa and Koichi Takayama and Yoichi Nakanishi",
year = "2007",
month = "8",
day = "1",
doi = "10.1136/jcp.2006.039396",
language = "English",
volume = "60",
pages = "916--920",
journal = "Journal of Clinical Pathology - Clinical Molecular Pathology",
issn = "0021-9746",
publisher = "BMJ Publishing Group",
number = "8",

}

TY - JOUR

T1 - Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis

AU - Yamada, Mizuho

AU - Kuwano, Kazuyoshi

AU - Maeyama, Takashige

AU - Yoshimi, Michihiro

AU - Hamada, Naoki

AU - Fukumoto, Jutaro

AU - Egashira, Kensuke

AU - Hiasa, Kenichi

AU - Takayama, Koichi

AU - Nakanishi, Yoichi

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34547755121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547755121&partnerID=8YFLogxK

U2 - 10.1136/jcp.2006.039396

DO - 10.1136/jcp.2006.039396

M3 - Article

C2 - 17018685

AN - SCOPUS:34547755121

VL - 60

SP - 916

EP - 920

JO - Journal of Clinical Pathology - Clinical Molecular Pathology

JF - Journal of Clinical Pathology - Clinical Molecular Pathology

SN - 0021-9746

IS - 8

ER -