Cited by 191Prenatal Substance Exposure EffectsNeonatal Respiratory Health ResearchSmoking Behavior and Cessation

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Maternal Nicotine Exposure Upregulates Collagen Gene Expression in Fetal Monkey Lung

Sekhon, Harmanjatinder S., Keller, Jennifer A., Proskocil, Becky J., Martin, Ellen L., Spindel, Eliot R.·2002·American Journal of Respiratory Cell and Molecular Biology

DOI 10.1165/ajrcmb.26.1.4170

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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 α 7 nAChR and collagen to the same cells in airway wall cells, and colocalization of α 7 nAChR and collagen was confirmed in isolated pulmonary fibroblasts. These findings suggest that nicotine may directly interact with α 7 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.

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Authors: Sekhon, H. S., Keller, J. A., Proskocil, B. J., Martin, E. L., & Spindel, E. R.
Affiliations: Oregon Health & Science University (US)
ORCID: Keller, Jennifer A.
Proskocil, Becky J.
Spindel, Eliot R.
Venue: American Journal of Respiratory Cell and Molecular Biology
Publisher: Oxford University Press (OUP)
Published: 2002-01-01
Volume: 26
Issue: 1
Pages: 31-41
ISSN: 1044-1549 (ISSN-L)
1535-4989
DOI: 10.1165/ajrcmb.26.1.4170
OpenAlex: W1914845986
Cited by: 191
References: 34
Citations by year: 2026: 5 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 10 · 2017: 9 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 4 · 2012: 15
FWCI: 8.78
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
PubMed (publishedVersion)
Funders: National Center for Research Resources (RR-00163.)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD/HL-37131)
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: maternal nicotine exposure, alpha7 nicotinic acetylcholine receptor, collagen gene expression, type I collagen, type III collagen, elastin, lung fibroblasts, fetal lung development, airway wall thickening, smoking during pregnancy, rhesus monkeys
MeSH terms: Animals, Bungarotoxins, Cells, Cultured, Collagen, Dose-Response Relationship, Drug, Female, Fibroblasts, Humans, Immunohistochemistry, Lung, Macaca mulatta, Nicotine, Pregnancy, Protein Binding, Pulmonary Alveoli, Receptors, Nicotinic, RNA, Messenger, Smoking, Time Factors, Up-Regulation, In Situ Hybridization, Nicotinic Agonists, Maternal Exposure, Reverse Transcriptase Polymerase Chain Reaction, alpha7 Nicotinic Acetylcholine Receptor

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Maternal Nicotine Exposure Upregulates Collagen Gene Expression in Fetal Monkey Lung

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