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

M. Shiratori, G. Michalopoulos, H. Shinozuka, Gurmukh Singh, H. Ogasawara, S. L. Katyal

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume12
Issue number2
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Alveolar Epithelial Cells
Hepatocyte Growth Factor
DNA
Fibroblast Growth Factor 1
Lung
Transforming Growth Factor alpha
Epidermal Growth Factor
Transforming Growth Factor beta
Thymidine
Messenger RNA
Proto-Oncogene Proteins c-met
In Vitro Techniques
Primary Cell Culture
Proto-Oncogenes
Pancreatic Elastase
Cell proliferation
Bromodeoxyuridine
Mitogens
Northern Blotting
Labeling

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Hepatocyte growth factor stimulates DNA synthesis in alveolar epithelial type II cells in vitro. / Shiratori, M.; Michalopoulos, G.; Shinozuka, H.; Singh, Gurmukh; Ogasawara, H.; Katyal, S. L.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 12, No. 2, 01.01.1995, p. 171-180.

Research output: Contribution to journalArticle

Shiratori, M. ; Michalopoulos, G. ; Shinozuka, H. ; Singh, Gurmukh ; Ogasawara, H. ; Katyal, S. L. / Hepatocyte growth factor stimulates DNA synthesis in alveolar epithelial type II cells in vitro. In: American Journal of Respiratory Cell and Molecular Biology. 1995 ; Vol. 12, No. 2. pp. 171-180.
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