The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Maternal Nicotine Exposure Upregulates Collagen Gene Expression in Fetal Monkey Lung
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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“Prenatal nicotine exposure leads to thickening of walls surrounding airways and pulmonary vessels in animal models,(209, 210) a finding that has also been reported in the human offspring of smokers,(211, 212) along with similar increases in connective tissue and α7 expression.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [209]
In the citing paper
“Treatment of pregnant rhesus monkeys with nicotine causes marked increases of levels of α7 nAChR in fibroblasts surrounding airways and blood vessels in the fetal monkey lung, and increases in collagen in a similar distribution.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [209]
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Citations
Cites
Pharmacologic Aspects of Cigarette Smoking and Nicotine Addiction
Oates, J. A., Wood, A. J. J., & Benowitz, N. L. (1988) · New England Journal of Medicine · doi:10.1056/nejm198811173192005 · Cited by 969
Benowitz, N. L., & Gourlay, S. G. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00079-x · Cited by 529
The Effect of Maternal Smoking during Pregnancy on Early Infant Lung Function
Hanrahan, J. P., Tager, I. B., Segal, M. R., Tosteson, T. D., Castile, R. G., Vunakis, H. V., Weiss, S. T., & Speizer, F. E. (1992) · American Review of Respiratory Disease · doi:10.1164/ajrccm/145.5.1129 · Cited by 527
Schoepfer, R., Conroy, W. G., Whiting, P. J., Gore, M., & Lindstrom, J. M. (1990) · Neuron · doi:10.1016/0896-6273(90)90031-a · Cited by 473
Luck, W., Nau, H., Hansen, R., & Steldinger, R. (2017) · Developmental Pharmacology and Therapeutics · doi:10.1159/000457063 · Cited by 444
Nicotinic acetylcholine receptors in health and disease
Lindstrom, J. (1997) · Molecular Neurobiology · doi:10.1007/bf02740634 · Cited by 443
Lung Function, Pre- and Post-natal Smoke Exposure, and Wheezing in the First Year of Life
Tager, I. B., Hanrahan, J. P., Tosteson, T. D., Castile, R. G., Brown, R. W., Weiss, S. T., & Speizer, F. E. (1993) · American Review of Respiratory Disease · doi:10.1164/ajrccm/147.4.811 · Cited by 315
Sekhon, H. S., Jia, Y., Raab, R., Kuryatov, A., Pankow, J. F., Whitsett, J. A., Lindstrom, J., & Spindel, E. R. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5232 · Cited by 311
Self-citationMaternal Smoking During Pregnancy. Effects on Lung Function During the First 18 Months of Life
Tager, I. B., Ngo, L. H., & Hanrahan, J. P. (1995) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.152.3.7663813 · Cited by 304
In utero exposure to cigarette smoking influences lung function at birth
Carlsen, K. L., Jaakkola, J. J. K., Nafstad, P. H. J., & Carlsen, K.-H. (1997) · European Respiratory Journal · doi:10.1183/09031936.97.10081774 · Cited by 260
Cited by
Sorted by citations
Acetylcholine beyond neurons: the non‐neuronal cholinergic system in humans
Wessler, I. K., & Kirkpatrick, C. J. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.185 · Cited by 872
Risk factors and early origins of chronic obstructive pulmonary disease
Postma, D. S., Bush, A., & van den Berge, M. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60446-3 · Cited by 539
Long-Term Consequences of Fetal and Neonatal Nicotine Exposure: A Critical Review
Bruin, J. E., Gerstein, H. C., & Holloway, A. C. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq103 · Cited by 379
Nicotine and the Developing Human
England, L. J., Bunnell, R. E., Pechacek, T. F., Tong, V. T., & McAfee, T. A. (2015) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2015.01.015 · Cited by 320
Neuman, Å., Hohmann, C., Orsini, N., Pershagen, G., Eller, E., Kjaer, H. F., Gehring, U., Granell, R., Henderson, J., Heinrich, J., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201203-0501oc · Cited by 260
Metadata
- Authors
- Sekhon, H. S., Keller, J. A., Proskocil, B. J., Martin, E. L., & Spindel, E. R.
- Affiliations
- Oregon Health & Science University (US)
- 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
- 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
- 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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