Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung: Association with α7 nicotinic acetylcholine receptors

H. S. Sekhon, J. A. Keller, B. J. Proskocil, E. L. Martin, Eliot Spindel

    Research output: Contribution to journalArticle

    148 Citations (Scopus)

    Abstract

    The recent identification of nicotinic acetylcholine receptors (nAChR) in pulmonary fibroblasts suggests that in utero nicotine exposure may alter collagen expression by these cells in the developing lung. To test this hypothesis, timed-pregnant rhesus monkeys were administered nicotine (1-1.5 mg/kg/d, subcutaneously) using osmotic minipumps from Days 26-134 or 26-160 of gestation (term = 165 d). In utero nicotine exposure significantly increased airway wall area per unit epithelial basement membrane. Collagen type I and III mRNA expression and immunostaining were significantly increased in the airway and alveolar walls of the nicotine-treated group. Elastin mRNA expression increased, but protein expression in parenchyma remained unchanged. Dual labeling studies colocalized α7 nAChR and collagen to the same cells in airway wall cells, and colocalization of α7 nAChR and collagen was confirmed in isolated pulmonary fibroblasts. These findings suggest that nicotine may directly interact with α7 nAChR to increase collagen accumulation in airway and alveolar walls following in utero nicotine exposure. These data suggest that passage of nicotine across the placenta to increase collagen deposition and therefore increase airway wall dimensions in fetal lung may partially explain the observed alterations in lung mechanics in the infants of mothers who smoke during pregnancy.

    Original languageEnglish (US)
    Pages (from-to)31-41
    Number of pages11
    JournalAmerican Journal of Respiratory Cell and Molecular Biology
    Volume26
    Issue number1
    StatePublished - 2002

    Fingerprint

    Maternal Exposure
    Nicotinic Receptors
    Nicotine
    Gene expression
    Haplorhini
    Up-Regulation
    Collagen
    Gene Expression
    Lung
    Fibroblasts
    Pregnancy
    Messenger RNA
    Collagen Type III
    Elastin
    Collagen Type I
    Mechanics
    Macaca mulatta
    Basement Membrane
    Smoke
    Cell Wall

    ASJC Scopus subject areas

    • Cell Biology
    • Molecular Biology
    • Pulmonary and Respiratory Medicine

    Cite this

    Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung : Association with α7 nicotinic acetylcholine receptors. / Sekhon, H. S.; Keller, J. A.; Proskocil, B. J.; Martin, E. L.; Spindel, Eliot.

    In: American Journal of Respiratory Cell and Molecular Biology, Vol. 26, No. 1, 2002, p. 31-41.

    Research output: Contribution to journalArticle

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