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. AIMS: 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.
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. AIMS: 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.
Authors: J F Pittet; M J Griffiths; T Geiser; N Kaminski; S L Dalton; X Huang; L A Brown; P J Gotwals; V E Koteliansky; M A Matthay; D Sheppard Journal: J Clin Invest Date: 2001-06 Impact factor: 14.808
Authors: T Maeyama; K Kuwano; M Kawasaki; R Kunitake; N Hagimoto; N Hara Journal: Am J Physiol Lung Cell Mol Physiol Date: 2001-06 Impact factor: 5.464
Authors: Sun Kyung Kim; Lindsey Barron; Cynthia S Hinck; Elyse M Petrunak; Kristin E Cano; Avinash Thangirala; Brian Iskra; Molly Brothers; Machell Vonberg; Belinda Leal; Blair Richter; Ravindra Kodali; Alexander B Taylor; Shoucheng Du; Christopher O Barnes; Traian Sulea; Guillermo Calero; P John Hart; Matthew J Hart; Borries Demeler; Andrew P Hinck Journal: J Biol Chem Date: 2017-02-22 Impact factor: 5.157