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Double intratracheal instillation of keratinocyte growth factor prevents bleomycin‐induced lung fibrosis in rats
Author(s) -
Sugahara Kazuhiro,
Iyama KenIchi,
Kuroda Marcelo J.,
Sano Kimihiko
Publication year - 1998
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199809)186:1<90::aid-path137>3.0.co;2-x
Subject(s) - bleomycin , intratracheal instillation , pulmonary fibrosis , fibrosis , lung , lung fibrosis , medicine , keratinocyte , pathology , cancer research , chemistry , chemotherapy , in vitro , biochemistry , bronchoalveolar lavage
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 μg/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. © 1998 John Wiley & Sons, Ltd.