Expression of genes coding for growth factors in experimental pneumoconiosis

Our plain-English summary of Expression of genes coding for growth factors in experimental pneumoconiosis, by G.F. Morris, J.Y. Liu, W.H. Lei, et al (Chest, 1996).

The study

• Authors: G.F. Morris, J.Y. Liu, W.H. Lei, A.R. Brody
• Journal: Chest
• Published: 1996;109(3 Suppl):45S-49S
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

The authors called this conference article a review of rat lung responses to inhaled asbestos, with preliminary data from their laboratory. The type of asbestos used is not named. Rats received one 5-hour exposure to an asbestos aerosol, and lungs were tested for activity of the gene for platelet-derived growth factor A (PDGF-A), which drives cell growth. Preliminary results suggested the gene was active in macrophages, epithelial and interstitial cells where fibers settled, but not in unexposed rats or tissue away from lesions. Lung PDGF-A messenger RNA rose approximately 12-fold during exposure, a figure the authors said must be verified. TGF-beta (citing an earlier publication) and TGF-alpha (unpublished data) were also detected at developing scar sites. In cultured rat embryo fibroblasts given a human PDGF-A promoter linked to a reporter gene, asbestos lowered absolute reporter output, which the authors said was consistent with toxicity. Relative to an internal control, reporter output rose twofold to threefold (the figure legend says threefold to fourfold), in a single experiment. The authors concluded that inhaled asbestos rapidly induces growth factors that could mediate fibrosis.

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: Review (conference supplement) that also reports preliminary results from the authors' own animal experiments in rats and cell-culture experiments
• Who was studied: Rats given a single inhalation exposure to asbestos (number of animals not stated), and a rodent cell line of cloned rat embryo fibroblasts (CREF) grown in culture
• Exposure: Asbestos fibers (type not named in the article). Rats breathed an aerosol for 5 hours at a concentration that is garbled in the scanned text (printed as "10 mglmm3"). Cultured CREF cells carrying a transfected human PDGF-A promoter reporter construct were exposed to 5 micrograms per square centimeter of asbestos for 18 hours. Nonfibrogenic carbonyl iron particles were used as a comparison in the cell assay.
• Main results:
  • In exposed rats, preliminary in situ hybridization results suggested that the PDGF-A gene was expressed in macrophages, epithelial cells and interstitial cells at the sites of fiber deposition
  • Tissue from unexposed control rats, and alveolar walls away from the developing lesions in exposed rats, were negative for PDGF expression (data not shown)
  • Preliminary data suggested that PDGF-A messenger RNA in the lungs of exposed rats increased approximately 12-fold during the 5-hour exposure period, compared with unexposed rats
  • Immunohistochemistry detected transforming growth factor beta (TGF-beta) and TGF-alpha at the sites of the developing fibrotic scar in the rat asbestosis model. The TGF-beta finding is cited to an earlier publication; the TGF-alpha finding is attributed to unpublished data.
  • In CREF cells transfected with a human PDGF-A promoter reporter construct, asbestos at 5 micrograms per square centimeter increased reporter expression twofold to threefold relative to the internal control, according to the main text. The Figure 3 legend states a threefold to fourfold increase.
  • The absolute output of the transfected PDGF promoter reporter declined in CREF cells exposed to asbestos for 18 hours, compared with unexposed cells. The authors said the reduction in both reporter and control output is consistent with the observation that high levels of asbestos are toxic to CREF cells.
  • Reporter expression from a comparison promoter (SV40 early promoter) did not change relative to the internal control with asbestos treatment
  • Other experiments suggested that nonfibrogenic carbonyl iron particles did not activate PDGF reporter expression in the cell assay (data not shown)
• The authors' conclusion: The authors stated that their data demonstrate that inhalation exposure of rats to fibrogenic asbestos fibers induces expression of a variety of growth factors that could mediate the fibrosis that follows inflammation. They also stated that the cellular response to fiber deposition is extremely rapid.
• Limitations the authors state:
  • The magnitude of the approximately 12-fold increase in PDGF-A messenger RNA must be verified by future experiments
  • The in situ hybridization results were preliminary, and the complete analyses were to be published elsewhere
  • The cell-culture reporter results came from a single experiment performed with duplicate samples
  • Other inhaled agents may produce slightly different cellular and molecular responses than asbestos

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis.

Related studies

• 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)
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)
• Rapid activation of PDGF-A and -B expression at sites of lung injury in asbestos-exposed rats — J.Y. Liu, G.F. Morris, et al. (1997)
• 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)
• Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro — D.M. Brass, S.Y. Tsai, et al. (2001)
• Laser capture microdissection reveals dose-response of gene expression in situ consequent to asbestos exposure — Q. Yin, A.R. Brody, et al. (2007)

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