HEPATOCYTE GROWTH-FACTOR MAY ACT AS A PULMOTROPHIC FACTOR ON LUNG REGENERATION AFTER ACUTE LUNG INJURY

Hepatocyte growth factor (HGF) has been shown to have hepatotrophic an d renotropic functions for regeneration of the liver and kidney throug h its mitogenic, motogenic, and morphogenic properties. To examine the involvement of HGF in lung regeneration after acute injury, we analyz ed changes of HGF mRNA, HGF activity, and HGF receptors in the rat lun g after lung insult and measured HGF concentration in sera of patients with various lung diseases. Following the onset of acute lung injury induced by intratracheal hydrochloride injection, a compensatory DNA s ynthesis occurred in the bronchial epithelium with a peak at 24 h and in the alveolar epithelium with a peak at 48 h. Expression of HGF mRNA in the rat lung remarkably increased only 3 h after the treatment and HGF activity in the lung also increased to about 3-fold at 6 h later. HGF receptors in the lung but not in the other noninjured organs were down-regulated 12 h later. These marked increases in HGF mRNA and HGF activity and the concomitant down-regulation of HGF receptor occurred before the marked compensatory DNA synthesis in bronchial and alveola r epithelial cells. HGF concentration in sera of patients with various lung diseases, as measured by radioimmunoassay, was much higher than that in healthy donors. These results suggest that HGF is newly produc ed in the lung after acute lung injury and may have a role in regenera tion of the lung.