In vivo mitogenic action of HGF on lung epithelial cells: pulmotrophic role in lung regeneration

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 HGF levels are elevated in blood of patients with lung diseases. To search for a possible pulmotrophic function of HGF in lung regeneration, we 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 micrograms.mouse-1.day-1) into mice with acute lung injury induced by the intratracheal infusion of 10 mM HCI stimulated DNA synthesis of airway epithelial cells to levels threefold higher than those in mice with no HGF-injections, but it did not stimulate DNA synthesis of alveolar epithelial cells. However, HGF injection at higher dose (100 micrograms.mouse-1.day-1) 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.