title: Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice.
abstract: Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema.
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tobinaga
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Katsuro
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Abo
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamasaki
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
keywords: elastase; electroporation; emphysema; gene therapy; keratinocyte growth factor