Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis.
BACKGROUND
Transforming growth factor-beta1 (TGF-beta1) has the potential to induce acute inflammation and apoptosis in lung epithelial cells and plays a central role in subsequent fibrosis.


OBJECTIVE
To examine a new anti-TGF-beta1 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-beta1 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-beta1 strategy may have clinical application in the treatment of lung injury and fibrosis.
Yamada
Mizuho
M
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kuwano
Kazuyoshi
K
Maeyama
Takashige
T
Yoshimi
Michihiro
M
Hamada
Naoki
N
Fukumoto
Jutaro
J
Egashira
Kensuke
K
Hiasa
Kenichi
K
Takayama
Koichi
K
Nakanishi
Yoichi
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis / Q000235:genetics; D001761:Bleomycin; D004195:Disease Models, Animal; D018274:Electroporation / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D020287:In Situ Nick-End Labeling / Q000379:methods; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012995:Solubility; D014162:Transfection / Q000379:methods; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
D000903:Antibiotics, Antineoplastic; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001761:Bleomycin