Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice
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 K...
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JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491498/ |
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pubmed-44914982015-07-09 Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice Tobinaga, Shuichi Matsumoto, Keitaro Nagayasu, Takeshi Furukawa, Katsuro Abo, Takafumi Yamasaki, Naoya Tsuchiya, Tomoshi Miyazaki, Takuro Koji, Takehiko Regular Article 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. JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 2015-06-29 2015-06-18 /pmc/articles/PMC4491498/ /pubmed/26160987 http://dx.doi.org/10.1267/ahc.15004 Text en 2015 The Japan Society of Histochemistry and Cytochemistry This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Tobinaga, Shuichi Matsumoto, Keitaro Nagayasu, Takeshi Furukawa, Katsuro Abo, Takafumi Yamasaki, Naoya Tsuchiya, Tomoshi Miyazaki, Takuro Koji, Takehiko |
| spellingShingle |
Tobinaga, Shuichi Matsumoto, Keitaro Nagayasu, Takeshi Furukawa, Katsuro Abo, Takafumi Yamasaki, Naoya Tsuchiya, Tomoshi Miyazaki, Takuro Koji, Takehiko Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice |
| author_facet |
Tobinaga, Shuichi Matsumoto, Keitaro Nagayasu, Takeshi Furukawa, Katsuro Abo, Takafumi Yamasaki, Naoya Tsuchiya, Tomoshi Miyazaki, Takuro Koji, Takehiko |
| author_sort |
Tobinaga, Shuichi |
| title |
Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice |
| title_short |
Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice |
| title_full |
Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice |
| title_fullStr |
Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice |
| title_full_unstemmed |
Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice |
| title_sort |
keratinocyte growth factor gene electroporation into skeletal muscle as a novel gene therapeutic approach for elastase-induced pulmonary emphysema in mice |
| description |
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. |
| publisher |
JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491498/ |
| _version_ |
1613243962211958784 |