In vivo mitogenic action of hepatocyte growth factor on lung
epithelial cells: pulmotrophic role in lung regeneration.
Ohmichi, Hidenori, Kunio Matsumoto, Toshikazu Nakamura.
Division of Biochemistry, Department of Oncology, Biomedical
Research Center, Osaka University Medical School, Suita, Osaka 565,
Japan
APStracts 3:0004L, 1996.
Hepatocyte growth factor (HGF) has mitogenic, morphogenic, and
motogenic activities on epithelial cells, and plays important roles
in regeneration of the liver and the kidney. We previously found that
the expression of HGF gene is rapidly induced in the lung after acute
lung injury in experimental animals and that blood HGF levels are
elevated in patients with lung diseases. To search for a possible
pulmotrophic function of HGF in lung regeneration, we here examined
the mitogenic activity of HGF on tracheal epithelial cells, in vitro,
and evaluated the efficacy of HGF-administration on lung regeneration
after acute lung injury in mice. HGF markedly stimulated
proliferation and DNA synthesis of rat tracheal epithelial cells in
primary culture in a dose-dependent manner. The intravenous injection
of human recombinant HGF (10 [mu]g/mouse/day) into mice with acute
lung injury induced by the intratracheal infusion of 10 mM HCl,
stimulated DNA synthesis of airway epithelial cells to levels 3-fold
higher than seen in mice with no HGF-injections, but it did not
stimulate DNA synthesis of alveolar epithelial cells. However, HGF
-injection at higher dose (100 [mu]g/mouse/day) stimulated DNA
synthesis of alveolar epithelial cells in vivo. These results
indicate that HGF is a potent mitogen for airway epithelial cells and
alveolar epithelial cells in vivo, as well as in vitro. HGF may act
as pulmotrophic factor responsible for airway and alveolar
regeneration, during lung regeneration after acute lung injury.
Received 17 May 1995; accepted in final form 8 December 1995.
APS Manuscript Number L152-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96