Double intratracheal instillation of keratinocyte growth factor prevents bleomycin-induced lung fibrosis in rats.
Alveolar re-epithelialization is necessary in the repair of damaged alveolar epithelium after lung injury. Keratinocyte growth factor (KGF) has been shown to be a potent proliferation and differentiation factor for rat alveolar type II cells. The present study examined whether KGF would prevent bleomycin-induced lung fibrosis. Adult rats were anaesthetized and recombinant human KGF (rhKGF) (150 micrograms/kg) or saline was injected intratracheally at 48 h before and 24 h after bleomycin (Bleo, 5 mg/kg) instillation. Seven and 14 days after the last administration, rat lungs were processed for lung physiology, immunohistochemistry, and in situ hybridization. Double instillation of KGF prevented the loss of body weight and reduction in total lung capacity (TLC) due to Bleo, and markedly attenuated the protein accumulation and mRNA expression of collagen types I and III and the decreased expression of surfactant protein mRNAs in the fibrotic lesions of Bleo-treated rats. KGF may play an important role in maintaining alveolar epithelium and repairing the damaged epithelium after lung injury.
Sugahara
K
K
Department of Anaesthesiology, Kumamoto University School of Medicine, Japan.
Iyama
K
K
Kuroda
M J
MJ
Sano
K
K
D000818:Animals; D001761:Bleomycin; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011347:Procollagen / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014109:Total Lung Capacity / Q000187:drug effects
C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D011347:Procollagen; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D001761:Bleomycin; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D003094:Collagen