title: Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat.
abstract: Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Katsuro
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto-Fukuda
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tobinaga
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Abo
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamasaki
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Kamohara
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nanashima
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Obatake
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: PCNA; compensatory growth; intratracheal injection; recombinant human KGF; trilobectomy