Hepatocyte growth factor is elevated in chronic lung injury and inhibits surfactant metabolism

Jeevalatha Vivekananda, Vibhudutta Awasthi, Shanjana Awasthi, Dolphin B. Smith, Richard J. King

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Adult respiratory distress syndrome may incorporate in its pathogenesis the-hyperplastic proliferation of alveolar epithelial type II cells and derangement in synthesis of pulmonary surfactant. Previous studies have demonstrated that hepatocyte growth factor (HGF) in the presence of serum is a potential mitogen for adult type II cells (R. J. Panos, J. S. Rubin, S. A. Aaronson, and R. J. Mason. J. Clin. Invest. 92: 969-977, 1993) and that it is produced by fetal mesenchymal lung cells (J. S. Rubin, A. M.-L. Chan, D. P. Botarro, W. H. Burgess, W. G. Taylor, A. C. Cech, D. W. Hirschfield, J. Wong, T. Miki, P. W. Finch, and S. A. Aaronson. Proc. Natl. Acad. Sci. USA 88; 415-419, 1991). In these studies, we expand on this possible involvement of HGF in chronic lung injury by showing the following. First, normal adult lung fibroblasts transcribe only small amounts of HGF mRNA, but the steady- state levels of this message rise substantially in lung fibroblasts obtained from animals exposed to oxidative stress. Second, inflammatory cytokines produced early in the injury stimulate the transcription of HGF in isolated fibroblasts, providing a plausible mechanism for the increased amounts of HGF seen in vivo. Third, HGF is capable of significantly inhibiting the synthesis and secretion of the phosphatidylcholines of pulmonary surfactant. Fourth, HGF inhibits the rate-limiting enzyme in de novo phosphatidylcholine synthesis, CTP:choline-phosphate cytidylyltransferase (EC Our data indicate that fibroblast-derived HGF could be partially responsible for the changes in surfactant dysfunction seen in adult respiratory distress syndrome, including the decreases seen in surfactant phosphatidylcholines.

Original languageEnglish (US)
Pages (from-to)L382-L392
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2 22-2
StatePublished - Feb 2000
Externally publishedYes


  • Adult respiratory distress syndrome
  • Cytidine 5'-triphosphate:choline-phosphate cytidylyltransferase
  • Phosphatidylcholine metabolism
  • Protein kinase A
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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