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Fibroproliferation in LPS-induced airway remodeling and bleomycin-induced fibrosis share common patterns of gene expression

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Abstract

Chronic LPS inhalation causes submucosal thickening and airway narrowing. To address the hypothesis that environmental airway disease is, in part, a fibroproliferative lung disease, we exposed C57BL/6 mice daily to LPS by inhalation for up to 2 months followed by 1 month of recovery. C57BL/6 mice exposed to daily inhaled LPS had significantly enhanced mRNA expression of TGF-β1, TIMP-1, fibronectin-1, and pro-collagen types I, III, and IV and show prominent submucosal expression of the myofibroblast markers desmin and α-smooth muscle actin. To further characterize global gene expression in airway fibroproliferation, we performed microarray analysis on total lung RNA from mice exposed to LPS both acutely and chronically. This analysis revealed a subset of genes typically associated with lung injury and repair, and ECM homeostasis. To further identify candidate genes specifically involved in generic fibroproliferation, we interrogated this analysis with genes induced in C57BL/6 mouse lung by bleomycin. This analysis yielded a list of 212 genes in common suggesting that there is a common subset of genes that regulate fibroproliferation in the lung independent of etiologic agent and site of injury.

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Authors and Affiliations

  1. Laboratory of Environmental Lung Diseases, National Heart, Lung and Blood Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA

    Ivana V. Yang, Holly Rutledge & David A. Schwartz

  2. Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    Marcus P. Kennedy

  3. Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA

    Gregory S. Whitehead & Lauranell H. Burch

  4. Department of Pediatrics/Neonatology, Duke University Medical Center, 403 Alex R. Sands Laboratory Building, DUMC 3373, Durham, NC, 27710, USA

    David M. Brass

Authors
  1. David M. Brass
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  2. Ivana V. Yang
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  3. Marcus P. Kennedy
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  4. Gregory S. Whitehead
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  5. Holly Rutledge
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  6. Lauranell H. Burch
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  7. David A. Schwartz
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Correspondence to David M. Brass.

Additional information

Brass and Yang contributed equally to this work and should be considered co-first authors.

This work was funded by the Department of Veterans’ Affairs (Merit Review), extramural grants (ES11375, ES07498, and ES09607), and the intramural research programs at NIEHS and NHLBI.

Electronic supplementary material

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Supplementary Table 1

Gene induction in the lung 1 week LPS (XLS 26 KB)

Supplementary Table 2

Gene induction in the lung in both chronic LPS (>2-fold) and bleomycin (XLS 30 KB)

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Brass, D.M., Yang, I.V., Kennedy, M.P. et al. Fibroproliferation in LPS-induced airway remodeling and bleomycin-induced fibrosis share common patterns of gene expression. Immunogenetics 60, 353–369 (2008). https://doi.org/10.1007/s00251-008-0293-3

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  • DOI: https://doi.org/10.1007/s00251-008-0293-3

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