Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro

Our plain-English summary of Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro, by D.M. Brass, S.Y. Tsai, A.R. Brody (Experimental Lung Research, 2001).

The study

• Authors: D.M. Brass, S.Y. Tsai, A.R. Brody
• Journal: Experimental Lung Research
• Published: 2001;27(8):639-53
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Lung fibroblasts are activated to proliferate and produce connective tissue during the development of lung fibrosis. The 129 mouse strain does not develop asbestos-induced fibrogenesis, whereas several other inbred strains rapidly respond to inhaled fibers. Thus, in the experiments presented here, we have compared the responses of primary lung fibroblasts isolated from 129 and C57BL/6 mice. The 129 and C57BL/6 mouse lung fibroblasts (MLFs) proliferated similarly in 10% fetal bovine serum (FBS), but after quiescence, the 129 MLFs grew more slowly in serum and responded less to the BB isoform of platelet-derived growth factor. This is consistent with our finding that the mRNA for the PDGF-a receptor exhibits reduced expression by the 129 MLFs compared to those from C57BL/6 mice. Fibroblasts from the SJL mouse strain, from a C57BL/6-129 hybrid, and from the 3T3 cell line all proliferated more vigorously than MLFs from the 129 mice. In addition, the 129 MLFs exhibited reduced expression of alpha1 procollagen mRNA consequent to treatment with tumor necrosisfactor alpha. Based on these new findings, we suggest that the reduced fibrogenesis in asbestos-exposed 129 mice is due to an intrinsic difference in the ability of the lung fibroblasts to respond to peptide growth factors.

In plain English

This laboratory study from Tulane University compared lung fibroblasts (connective-tissue cells) grown in culture from two mouse strains. One was the 129 strain, which the authors' earlier work had found does not develop asbestos-induced fibrotic lesions. The other was the C57BL/6 strain, which does. No asbestos was applied to the cells in these experiments. Before being rested in serum-free medium, fibroblasts from the mouse strains grew at comparable rates in 5% serum. After resting, 129 cells grew more slowly than cells from the other mice in 5% and 10% serum. With the growth factor PDGF-BB, C57BL/6 cell numbers doubled while 129 cell numbers did not change. C57BL/6 cells had about 3-fold the level of mRNA for the PDGF alpha receptor. TNF-alpha raised collagen-precursor mRNA in a dose-dependent way in both strains, but markedly less in 129 cells. The authors concluded it is possible that the 129 strain has an intrinsic, genetically programmed trait that makes it less able to respond to growth factors. They noted it is unknown whether cultured cells behave as they do in the animal.

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: In vitro laboratory experiment comparing primary lung fibroblasts cultured from different mouse strains (no asbestos exposure in these experiments)
• Who was studied: Primary lung fibroblasts isolated from 129, C57BL/6 and SJL inbred mice and a C57BL/6-129 F1 hybrid (mice from Jackson Labs), with Swiss 3T3 cells as a positive control; number of mice not stated; Tulane University Health Sciences Center, New Orleans
• Exposure: Cultured cells were treated with fetal bovine serum (1%, 5%, 10%), PDGF AA or PDGF BB at 20 ng/mL, and increasing concentrations of TNF-alpha. The 129 strain's resistance to asbestos comes from the authors' earlier animal work, not from this study.
• Main results:
  • Without a prior rest period, fibroblasts from the three inbred strains and the F1 hybrid grew at comparable rates in 5% serum.
  • Without a prior rest period, C57BL/6 fibroblasts grew at a reduced rate in 10% serum over 6 days.
  • After 2 days of quiescence in serum-free medium, 129 fibroblasts grew more slowly in serum than fibroblasts from C57BL/6, SJL and the hybrid. The figure legend reports this as significant (P less than .05).
  • In PDGF BB, 3T3 cells proliferated steadily, C57BL/6 fibroblast numbers doubled, and 129 fibroblast numbers did not change.
  • In PDGF AA, 3T3 cells proliferated moderately, C57BL/6 fibroblasts increased slightly, and 129 fibroblasts did not change.
  • Baseline mRNA for the PDGF alpha receptor in C57BL/6 fibroblasts was approximately 3-fold that in 129 fibroblasts.
  • TNF-alpha increased procollagen mRNA in a dose-dependent manner. The dose-response in 129 fibroblasts was markedly less robust than in C57BL/6 fibroblasts and 3T3 cells.
  • In preliminary experiments (data not shown), TGF-beta raised procollagen mRNA in fibroblasts from both strains. Expression in C57BL/6 cells appeared greater than in 129 cells but was not significantly different.
• The authors' conclusion: The authors concluded it is possible that the 129 strain has an intrinsic, genetically programmed characteristic that makes it less able to produce or respond to growth factors. In the abstract, they suggest this explains the reduced fibrogenesis seen in asbestos-exposed 129 mice.
• Limitations the authors state:
  • It is unknown whether the isolated fibroblasts keep the characteristics of their source strain and respond in culture as they would in the animal.
  • Quiescence in culture, with nutrients limited and mitogens removed, differs from normal growth arrest in the living lung.
  • Receptor differences were measured only at the mRNA level. Measuring the receptor proteins (by Western blotting) is needed to test the proposed mechanism.
  • The results cannot tell whether TNF-alpha acts on collagen directly or through TGF-beta.

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Fibrosis, Platelet-Derived Growth Factor (PDGF).

Related studies

• Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop — J.A. Lasky, P.G. Coin, et al. (1995)
• Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages — J.C. Bonner, A.R. Osornio-Vargas, et al. (1991)
• Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts — J.C. Bonner, A.L. Goodell, et al. (1993)
• Reduced tumor necrosis factor-alpha and transforming growth factor-beta1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure — D.M. Brass, G.W. Hoyle, et al. (1999)
• Early-passage rat lung fibroblasts do not migrate in vitro to transforming growth factor-beta — A.R. Osornio-Vargas, V.G. Kalter, et al. (1993)
• Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts — A.R. Osornio-Vargas, J.C. Bonner, et al. (1990)

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