Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors

Our plain-English summary of Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors, by I.Y. Adamson, J. Bakowska, H. Prieditis (American Journal of Respiratory Cell and Molecular Biology, 2000).

The study

• Authors: I.Y. Adamson, J. Bakowska, H. Prieditis
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2000;23(3):345-9
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The proliferative response of cultured pulmonary mesothelial cells (MCs) to epithelial cell mitogens such as keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) is investigated. A cell line of rat pleural MCs and freshly prepared rat visceral and parietal MCs were studied. Both KGF and HGF stimulated thymidine uptake in the cell line when cultured for 2 d in serum-free conditions; the growth increase was magnified when tumor necrosis factor (TNF)-alpha was also added to the cultures. Adding asbestos fibers alone to MCs in culture did not enhance DNA synthesis by these cells. The MCs were also shown to synthesize significant amounts of HGF but much less KGF when cultured for 2 d. When freshly prepared MCs were examined, normal cell growth was more rapid in the parietal cells, which also had a more epithelial-type morphology. The addition of HGF and KGF resulted in increased DNA synthesis in each cell type, but no effect of added TNF-alpha was found. The results indicate that pulmonary MCs have the potential to proliferate in response to cytokines such as HGF and KGF that are usually associated with epithelial cell regeneration after injury.

In plain English

In this laboratory study, the authors grew rat pleural mesothelial cells, the cells lining the chest cavity, in culture dishes. They used a commercial cell line and fresh visceral (lung-surface) and parietal (chest-wall) cells taken from male Sprague Dawley rats. They added two growth factors, hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), with or without tumor necrosis factor (TNF)-alpha. They also added crocidolite asbestos. They then measured DNA synthesis, a sign of cell division. In the cell line, HGF at 15 and 30 ng/ml raised uptake by 50%, and KGF at those doses gave significant increases. Adding TNF-alpha increased both effects further. Crocidolite at the lower doses did not increase DNA synthesis. At the highest dose, cell survival fell to 80% and DNA synthesis was lower. The cell line made 47.5 pg of HGF and 2.1 pg of KGF per million cells. Fresh visceral and parietal cells also increased DNA synthesis with HGF and KGF, but TNF-alpha had no significant effect on them. The authors concluded that these cells can potentially multiply in response to HGF and KGF. They stated that how this relates to tumor development in living animals is not known.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell culture experiment
• Who was studied: A commercial rat pleural mesothelial cell line (CCL 216), plus fresh visceral and parietal mesothelial cells prepared from male Sprague Dawley rats; the number of rats is not stated
• Exposure: HGF and KGF at 5, 15 and 30 ng/ml, with or without TNF-alpha at 15 or 30 ng. Crocidolite asbestos was added for 2 days at two doses, printed as 1 or 10 mg/ml (0.5 or 5 mg/cm2).
• Main results:
  • Cell line: HGF at 15 and 30 ng/ml produced a 50% increase in thymidine uptake compared with serum-free controls
  • Cell line: TNF-alpha alone at 30 ng gave a 25% increase in uptake; combined with HGF it gave a further increase over HGF alone
  • Cell line: KGF at 15 and 30 ng significantly increased DNA synthesis, and the effect was augmented by TNF-alpha
  • Cell line: at crocidolite doses up to and including 1.0 (as printed, mg/ml), cell viability was 95 to 98% and DNA synthesis did not increase
  • Cell line: at the higher crocidolite dose, viability fell to 80% and DNA synthesis was lower
  • The cell line contained 47.5 pg of HGF per million cells after 2 days, not increased by TNF-alpha
  • The cell line made only 2.1 pg of KGF per million cells, unchanged by TNF-alpha
  • Fresh parietal cells reached confluence in about 1 week, visceral cells in 10 to 14 days
  • Fresh visceral cells showed increased thymidine uptake at the higher dose of HGF and KGF
  • Fresh parietal cells responded particularly to both doses of HGF
  • In fresh cells, TNF-alpha caused no significant change in thymidine uptake
• The authors' conclusion: The authors concluded that pulmonary mesothelial cells have the potential to proliferate in response to HGF and KGF. Because adding asbestos directly did not increase DNA synthesis, they suggested that the early growth of these cells after asbestos deposition may not be a direct effect of fibers.
• Limitations the authors state:
  • The properties of the cell line may have changed with repeated passage, which is why fresh cells were also tested
  • How these laboratory findings relate to tumor development in living animals is not known

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Necrosis, Cytokine.

Related studies

• KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos — I.Y. Adamson, J. Bakowska (2001)
• Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture — E. Bermudez, J. Everitt, et al. (1990)
• Hepatocyte growth factor/scatter factor enhances the invasion of mesothelioma cell lines and the expression of matrix metalloproteinases — P. Harvey, I.M. Clark, et al. (2000)
• Fibroblast growth factor-10 prevents asbestos-induced alveolar epithelial cell apoptosis by a mitogen-activated protein kinase-dependent mechanism — D. Upadhyay, V. Panduri, et al. (2005)
• Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas — L.A. Goodglick, C.A. Vaslet, et al. (1997)
• Differential responses to growth factors by normal human mesothelial cultures from individual donors — J.F. Lechner, M.A. LaVeck, et al. (1989)

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