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Expression of lynx1 in developing lung and its modulation by prenatal nicotine exposure

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Abstract

The expression of nicotinic acetylcholine receptors (nAChR) in fetal lung suggests maternal smoking during pregnancy effects newborn lung structure and function by the direct interaction of nicotine with nAChR in the developing lung. The recent identification of the lynx1 nAChR modulator protein in nicotinic neurons in the brain suggests that lynx1 may be similarly expressed in the lung. To study this, cDNAs encoding lynx1 were cloned from rhesus monkey lung. The temporal expression of lynx1 was studied in pre- and postnatal monkey lungs by in situ hybridization, immunohistochemistry, and realtime polymerase chain reaction (PCR). Lynx1 mRNA signal and lynx1 immunohistochemical staining were localized predominantly in airway epithelial cells, submucous glands, and smooth muscle cells, in endothelial and smooth muscle cells in vessel walls, and in alveolar type II cells. The distribution of lynx1 was similar to that of α4, β2, and β4 nAChR expression as determined by immunohistochemistry. Immunohistochemical staining also co-localized choline acetyltransferase, the enzyme that synthesizes acetylcholine, with lynx1 expression. Lynx1 expression was first observed in 71-day fetal lungs and increased with age. Immunohistochemistry, Western analysis, and realtime PCR analysis showed increased lynx1 expression in lungs following prenatal nicotine exposure. Thus, lynx1 is co-expressed with nAChR in the lung. Alteration of lynx1 levels is a potential new mechanism by which nicotine affects lung development.

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Acknowledgements

We thank Dr. Anda Cornea for assistance with confocal microscopy, Jen Spindel and Courtney Gravett for assistance with immunohistochemistry, Dr. Jeff Whitsett for generously providing the pro-SP-B antibody, and the Oregon National Primate Research Center Division of Animal Resources for assistance with timed-pregnant monkeys.

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Authors and Affiliations

  1. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR, 97006, USA

    Harmanjatinder S. Sekhon, Pingfang Song, Yibing Jia & Eliot R. Spindel

  2. Department of Pathology, Harborview Medical Center, Seattle, WA, 98104, USA

    Harmanjatinder S. Sekhon

  3. Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Jon Lindstrom

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  1. Harmanjatinder S. Sekhon
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  2. Pingfang Song
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  3. Yibing Jia
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  4. Jon Lindstrom
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  5. Eliot R. Spindel
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Correspondence to Eliot R. Spindel.

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This research was supported by National Institute of Health grants RR-00163 and HD/HL-37131.

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Sekhon, H.S., Song, P., Jia, Y. et al. Expression of lynx1 in developing lung and its modulation by prenatal nicotine exposure. Cell Tissue Res 320, 287–297 (2005). https://doi.org/10.1007/s00441-005-1077-9

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  • DOI: https://doi.org/10.1007/s00441-005-1077-9

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