Document Detail


In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism.
MedLine Citation:
PMID:  17215434     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We recently suggested that alveolar interstitial fibroblast-to-myofibroblast transdifferentiation may be a key mechanism underlying in utero nicotine-induced lung injury. However, the effects of in utero nicotine exposure on fetal alveolar type II (ATII) cells have not been fully determined. Placebo, nicotine (1 mg/kg), or nicotine (1 mg/kg) + the peroxisome proliferator-activated receptor (PPAR)-gamma agonist prostaglandin J(2) (PGJ(2), 0.3 mg/kg) was administered intraperitoneally once daily to time-mated pregnant Sprague-Dawley rats from embryonic day 6 until their death on embryonic day 20. Fetal ATII cells were isolated, and ATII cell proliferation, differentiation (surfactant synthesis), and metabolism (metabolic profiling with the stable isotope [1,2-(13)C(2)]-d-glucose) were determined after nicotine exposure in utero or in vitro. In utero nicotine exposure significantly stimulated ATII cell proliferation, differentiation, and metabolism. Although the effects on ATII cell proliferation and metabolism were almost completely prevented by concomitant treatment with PGJ(2), the effects on surfactant synthesis were not. On the basis of in utero and in vitro data, we conclude that surfactant synthesis is stimulated by nicotine's direct effect on ATII cells, whereas cell proliferation and metabolism are affected via a paracrine mechanism(s) secondary to its effects on the adepithelial fibroblasts. These data provide evidence for direct and indirect effects of in utero nicotine exposure on fetal ATII cells that could permanently alter the "developmental program" of the developing lung. More importantly, concomitant administration of PPAR-gamma agonists can effectively attenuate many of the effects of in utero exposure to nicotine on ATII cells.
Authors:
Virender K Rehan; Ying Wang; Sharon Sugano; Jamie Santos; Sanjay Patel; Reiko Sakurai; Laszlo G Boros; Laszlo W Boros; W-P Lee; John S Torday
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  292     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-02-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L323-33     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California-Los Angeles, 1124 West Carson St., Torrance, CA 90502, USA. vrehan@labiomed.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Female
Fetus / drug effects*,  metabolism,  pathology
Maternal-Fetal Exchange
Nicotine / administration & dosage,  toxicity*
PPAR gamma / agonists
Phospholipids / biosynthesis
Pregnancy
Prostaglandin D2 / analogs & derivatives,  pharmacology
Pulmonary Alveoli / drug effects*,  injuries,  metabolism,  pathology
Pulmonary Surfactant-Associated Protein B / biosynthesis
Rats
Rats, Sprague-Dawley
Smoking / adverse effects
Grant Support
ID/Acronym/Agency:
HL 075405/HL/NHLBI NIH HHS; HL 55268/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/PPAR gamma; 0/Phospholipids; 0/Pulmonary Surfactant-Associated Protein B; 41598-07-6/Prostaglandin D2; 54-11-5/Nicotine; 60203-57-8/9-deoxy-delta-9-prostaglandin D2
Comments/Corrections
Erratum In:
Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L820
Note: Boros, Laszlo W [corrected to Boros, Laszlo G]

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