Increase in the beta chain of hepatocyte growth factor (HGF beta) precedes c-met expression after bleomycin-induced lung injury in the rat.

After lung injury the regeneration of the alveolar epithelium is highly dependent on the proliferation of type II alveolar epithelial cells (AECs). Hepatocyte growth factor (HGF), a potent epithelial cell mitogen, is present as a single chain in normal tissue, but after injury HGF is converted to an active form composed of an alpha and a beta chain. In this study it was demonstrated that there was an increase in the beta chain of HGF 4 days after bleomycin administration, coinciding with the time of maximal type II AEC proliferation. Bronchoalveolar lavage fluid (BALF) obtained 4 days after bleomycin administration was maximally mitogenic to L2 cells, a nontransformed rat alveolar epithelial cell line. Type II cells isolated from normal rats do not express the HGF receptor, c-met. However, 4 days after bleomycin injury, using Western blot analysis, an increase in c-met was detected in AEC protein extracts. HGF induced c-met expression by L2 cells and neutralizing antibodies to HGF inhibited the mitogenic activity in the BALF. These findings suggest that HGF may regulate its own receptor on AECs and is an important mitogen for AECs 4 days after bleomycin administration.