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Hepatocyte Growth Factor Stimulates Migration of Type II Alveolar Epithelial Cells on the Provisional Matrix Proteins Fibronectin and Fibrinogen^*

^* From the University of Minnesota, Minneapolis, MN.

Correspondence to: H. J. Kim, MD, Pulmonary, Allergy, and Critical Care Medicine, University of Minnesota Medical School, 420 Delaware St SE, Box 276, Minneapolis, MN 55455

Survival following acute lung injury (ALI) depends on successful reepithelialization of the denuded alveolar basement membrane, a process that includes type II alveolar epithelial cell (AEC) migration on the provisional matrix proteins fibronectin and fibrinogen. We sought a therapeutic intervention that could accelerate type II AEC migration after ALI and thus promote alveolar healing. Since hepatocyte growth factor (HGF) is a potent mitogen for alveolar epithelial cells and a known motogen for other epithelial cells, we hypothesized that HGF stimulates AEC migration. The Boyden chemotaxis chamber was utilized to evaluate the migration of MP48 cells, a type II AEC line. Filters were coated on the bottom side with either fibronectin or fibrinogen. Immunofluorescence was performed to demonstrate whether these cells express HGF or keratinocyte growth factor (KGF) receptors. MP48 cells migrated on fibronectin, but migrated less on fibrinogen. HGF stimulated MP48 cell migration on both fibronectin and fibrinogen in a dose-dependent manner. HGF maximally stimulated migration on fibronectin by a factor of 9 (p = 0.954 by analysis of variance: trend for statistical significance) and migration on fibrinogen by a factor of 8 (p = 0.0233). Of note, KGF, a mitogen for AECs, did not stimulate migration. Immunofluorescence demonstrated the presence of both HGF and KGF receptors on these cells. Our results indicate that HGF augments type II AEC migration on provisional matrix proteins and thus may be beneficial in promoting alveolar repair following ALI.

Footnotes

Supported by NHLBI HL03576 (H.J.K.), NSF MCB9596838 (P.J.S.), NHLBI T32HL07741 (D.H.I.), and ALA Career Investigator Award (D.H.I.).

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