Lung

, Volume 187, Issue 5, pp 281–289

The Effects of Smoking on the Developing Lung: Insights from a Biologic Model for Lung Development, Homeostasis, and Repair

  • Virender K. Rehan
  • Kamlesh Asotra
  • John S. Torday
Article

DOI: 10.1007/s00408-009-9158-2

Cite this article as:
Rehan, V.K., Asotra, K. & Torday, J.S. Lung (2009) 187: 281. doi:10.1007/s00408-009-9158-2

Abstract

There is extensive epidemiologic and experimental evidence from both animal and human studies that demonstrates detrimental long-term pulmonary outcomes in the offspring of mothers who smoke during pregnancy. However, the molecular mechanisms underlying these associations are not understood. Therefore, it is not surprising that that there is no effective intervention to prevent the damaging effects of perinatal smoke exposure. Using a biologic model of lung development, homeostasis, and repair, we have determined that in utero nicotine exposure disrupts specific molecular paracrine communications between epithelium and interstitium that are driven by parathyroid hormone-related protein and peroxisome proliferator-activated receptor (PPAR)γ, resulting in transdifferentiation of lung lipofibroblasts to myofibroblasts, i.e., the conversion of the lipofibroblast phenotype to a cell type that is not conducive to alveolar homeostasis, and is the cellular hallmark of chronic lung disease, including asthma. Furthermore, we have shown that by molecularly targeting PPARγ expression, nicotine-induced lung injury can not only be significantly averted, it can also be reverted. The concept outlined by us differs from the traditional paradigm of teratogenic and toxicological effects of tobacco smoke that has been proposed in the past. We have argued that since nicotine alters the normal homeostatic epithelial-mesenchymal paracrine signaling in the developing alveolus, rather than causing totally disruptive structural changes, it offers a unique opportunity to prevent, halt, and/or reverse this process through targeted molecular manipulations.

Keywords

Nicotine Lung development Tobacco Smoking Chronic obstructive pulmonary disease Chronic lung disease 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Virender K. Rehan
    • 1
  • Kamlesh Asotra
    • 2
  • John S. Torday
    • 3
  1. 1.Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLADavid Geffen School of Medicine at UCLATorranceUSA
  2. 2.Tobacco-Related Disease Research Program, Office of the PresidentUniversity of CaliforniaOaklandUSA
  3. 3.Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLADavid Geffen School of Medicine at UCLATorranceUSA

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