Up-regulated expression of transforming growth factor-α in the bronchiolar-alveolar duct regions of asbestos-exposed rats

Jing Yao Liu, Gilbert F. Morris, Wei Hong Lei, Miriam Corti, Arnold R. Brody

    Research output: Contribution to journalArticlepeer-review

    74 Scopus citations

    Abstract

    It has become apparent that numerous growth factors and cytokines are produced during the development of fibroproliferative lung disease. Investigators must sort out which combinations of these factors are playing mechanistic roles in the disease process. Here we demonstrate that transforming growth factor (TGF)-α, a potent epithelial and mesenchymal cell mitogen, is up-regulated specifically at the sites of asbestos fiber deposition in the lungs of rats exposed for 5 hours. Unexposed animals and those exposed to high concentrations of iron spheres exhibited no increase in TGF-α expression at any time during the experiment. Inhaled asbestos fibers deposit initially at the bronchiolar-alveolar duct regions and alveolar macrophages accumulate at these sites within hours. Non-isotopic in situ hybridization and immunohistochemistry were used to show that the mRNA that codes for TGF-α along with the peptide were clearly up-regulated at the bronchiolar-alveolar duct regions by 24 hours after the single asbestos exposure. The numbers of labeled cells demonstrated that expression of the mRNA and protein remained significantly above background for at least 2 weeks after exposure along with increased cell proliferation assessed by staining for proliferating cell nuclear antigen. This, to our knowledge, is the first demonstration of TGF-α expression at sites of lung injury in developing fibroproliferative disease. This finding supports the hypothesis that the growth factor is involved in the dramatic epithelial and mesenchymal proliferation we documented previously, although additional experiments will be essential to establish the precise role of TGF-α.

    Original languageEnglish (US)
    Pages (from-to)205-217
    Number of pages13
    JournalAmerican Journal of Pathology
    Volume149
    Issue number1
    StatePublished - Jul 1996

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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