Expression of lynx1 in developing lung and its modulation by prenatal nicotine exposure.
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 alpha4, beta2, and beta4 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.
Sekhon
Harmanjatinder S
HS
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 97006, USA.
Song
Pingfang
P
Jia
Yibing
Y
Lindstrom
Jon
J
Spindel
Eliot R
ER
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D005629:Frozen Sections; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000196:embryology*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry*; D009538:Nicotine / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D009538:Nicotine; D002795:Choline O-Acetyltransferase