Hepatocyte growth factor stimulates DNA synthesis in alveolar epithelial type II cells in vitro

Am J Respir Cell Mol Biol. 1995 Feb;12(2):171-80. doi: 10.1165/ajrcmb.12.2.7532419.

Abstract

Hepatocyte growth factor (HGF) and its receptor, the product of c-MET proto-oncogene, are highly expressed in both fetal and adult lung, though their physiologic functions in the lung are largely unknown. In the present study, we examined whether alveolar type II cells in the lung are the target of HGF and whether HGF has any effects on growth of these cells. The alveolar epithelial type II cells were isolated from the lungs of adult male Sprague-Dawley rats by elastase digestion, and the cells were used to determine whether they express HGF and c-MET mRNAs and whether recombinant HGF has any effect on their DNA synthesis in primary culture. The effects were further compared with those induced by epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta 1 (TGF-beta 1). Northern blot analysis and in situ hybridization revealed that type II cells express c-MET mRNA but not HGF mRNA. HGF stimulated [3H]thymidine incorporation into type II cells in primary cultures. An increase was also seen in labeling index as determined by nuclear immunostaining of bromodeoxyuridine-incorporated DNA. While aFGF (200 ng/ml) exerted an effect comparable to HGF (25 ng/ml) on DNA synthesis in type II cells, EGF (20 ng/ml) and TGF-alpha (100 ng/ml) had lesser effects. TGF-beta 1, a potent inhibitor of epithelial cell proliferation, at 0.25 to 2 ng/ml, did not inhibit HGF-induced [3H]thymidine incorporation into type II cells. The results indicate that HGF exerts its effects on type II cells as a potent mitogen by a paracrine mode of action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • DNA / biosynthesis*
  • Epidermal Growth Factor / pharmacology
  • Epithelial Cells
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Fibroblast Growth Factor 1 / pharmacology
  • Gene Expression
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • In Vitro Techniques
  • Male
  • Proto-Oncogene Proteins c-met
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology
  • Thymidine / metabolism
  • Transforming Growth Factor alpha / pharmacology
  • Transforming Growth Factor beta / pharmacology

Substances

  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 1
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor
  • DNA
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases
  • Thymidine