title: Effect of adenovector-mediated gene transfer of keratinocyte growth factor on the proliferation of alveolar type II cells in vitro and in vivo.
abstract: Alveolar type II cell proliferation occurs after lung injury and is thought to minimize the subsequent fibrotic response. Keratinocyte growth factor (KGF) has been shown to be a potent growth factor for rat alveolar type II cells. In this study, we created a replication-deficient, recombinant human type 5 adenovirus vector expressing human KGF (Ad5-KGF) to produce alveolar type II cell hyperplasia in vivo. In rat type II cells in vitro, Ad5-KGF at a multiplicity of infection (MOI) of 2, 4, and 8 plaque-forming units (PFU)/cell increased thymidine incorporation 13.3-, 16.8-, and 20. 8-fold, respectively. The KGF concentration in the medium increased up to 26.0 +/- 1.0 ng/ ml. We then instilled 10(9) PFU of Ad5-KGF, Ad5-LacZ, or phosphate-buffered saline into Fischer 344 rats and analyzed the lungs 2, 3, 7, 14, 21, and 28 d later. Ad5-KGF produced extensive alveolar type II cell hyperplasia on Days 2, 3, and 7. Surfactant protein (SP)-A and SP-D in lavage and SP-D in serum increased more in the Ad5-KGF group than in the Ad5-LacZ and PBS groups on Days 2 and 3. KGF was readily detectable for up to 7 d in lavage fluid, although only a modest number of cells expressed KGF messenger RNA as detected by in situ hybridization. These data show that Ad5-KGF stimulates extensive alveolar type II cell proliferation in vivo.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA.
authors.forename: O
authors.initials: O
authors.lastname: Morikawa
authors.forename: T A
authors.initials: TA
authors.lastname: Walker
authors.forename: L D
authors.initials: LD
authors.lastname: Nielsen
authors.forename: T
authors.initials: T
authors.lastname: Pan
authors.forename: J L
authors.initials: JL
authors.lastname: Cook
authors.forename: R J
authors.initials: RJ
authors.lastname: Mason
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005822:Genetic Vectors; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000502:physiology*; D008297:Male; D051381:Rats; D014162:Transfection
chemical_list: C496453:FGF7 protein, human; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors