Keratinocyte growth factor decreases pulmonary edema, transforming growth factor-beta and platelet-derived growth factor-BB expression, and alveolar type II cell loss in bleomycin-induced lung injury.
Keratinocyte growth factor (KGF), a potent growth factor for type II pneumocytes and Clara cells, has been shown to prevent the end-stage pulmonary fibrosis and mortality in a rat model of bleomycin-induced lung injury. In this study, protective effects of KGF were explored during the earlier course of bleomycin-induced lung injury by studying protein exudation in alveolar edema fluids, pulmonary expression of transforming growth factor-beta (TGF beta) and platelet-derived growth factor-BB (PDGF-BB), and changes in type II pneumocytes and Clara cells after i.t. (intratracheal) bleomycin injection following KGF- or saline-pretreatment in rats. Total protein in bronchoalveolar lavage (BAL) fluids after bleomycin injury from KGF-pretreated rats was significantly lower than the levels in saline-pretreated rats. TGF beta protein in BAL fluids which peaked at day 3 after i.t. bleomycin in saline-pretreated lungs was not significantly increased at any time points in KGF-pretreated rats. PDGF-BB protein in whole lung tissues of KGF-pretreated rats also remained near normal throughout the course after i.t. bleomycin, in contrast to the significant increase in saline-pretreated rats. Numbers of type II pneumocytes and Clara cells in KGF-pretreated lungs after a high dose of bleomycin were close to the normal in intact lungs. At the same dose of bleomycin injury, type II pneumocytes in saline-pretreated lungs were markedly decreased, while the number of Clara cells in these rats was relatively preserved as the pre-injury level. In conclusion, KGF prevents bleomycin-induced end-stage pulmonary injury and mortality probably at least partly by decreasing protein-rich pulmonary edema, protein expression of fibrogenic cytokines TGF beta and PDGF-BB, and type II cell loss during the course of lung injury.
Yi
E S
ES
Department of Pathology, University of California, San Diego School of Medicine, USA.
Salgado
M
M
Williams
S
S
Kim
S J
SJ
Masliah
E
E
Yin
S
S
Ulich
T R
TR
D000818:Animals; D000077214:Becaplermin; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005122:Exudates and Transudates / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C496453:FGF7 protein, human; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D051523:Fibroblast Growth Factor 7; D000077214:Becaplermin; D005346:Fibroblast Growth Factors