Maternal Nicotine Exposure Induces Epithelial-Mesenchymal Transition in Rat Offspring Lungs.
BACKGROUND
Maternal nicotine exposure induces lung injuries and fibrosis in rat offspring. Epithelial-mesenchymal transition (EMT) following lung injury is a process in which epithelial cells mediate tissue repair.


OBJECTIVE
To determine the effects of maternal nicotine exposure on EMT in neonatal rat lungs.


METHODS
Nicotine was administered to pregnant Sprague-Dawley rats using a subcutaneous osmotic minipump that delivered a dose of 6 mg/kg/day on gestational days 7-21 or from gestational day 7 to postnatal day 14. A control group received an equal volume of saline.


RESULTS
The percentage of 8-hydroxy-2'-deoxyguanosine-positive cells in nuclear staining was significantly higher, the E-cadherin protein expression was significantly lower, and the N-cadherin protein expression was significantly higher in rats born to prenatal and postnatal nicotine-treated dams than in those born to prenatal saline- and nicotine-treated dams on postnatal day 7. These characteristics of EMT were associated with a significant increase in α-smooth muscle actin (SMA) expression on postnatal day 21. Rats born to prenatal and postnatal nicotine-treated dams showed significantly higher α-SMA expression and total collagen than those born to prenatal saline- and nicotine-treated dams on postnatal day 21. The number of cells expressing fibroblast-specific protein 1 and vimentin was higher in rats born to prenatal and postnatal nicotine-treated dams than in those born to prenatal saline- and nicotine-treated dams on postnatal days 7 and 21.


CONCLUSIONS
Maternal nicotine exposure during gestation and lactation induces EMT and contributes to lung fibrosis in rat offspring.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
Chung-Ming
CM
Chen
Hsiu-Chu
HC
Chou
Liang-Ti
LT
Huang
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000276:immunology; D003094:Collagen / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D007774:Lactation; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D018811:Maternal Exposure / Q000009:adverse effects*; D009538:Nicotine / Q000008:administration & dosage*; D011247:Pregnancy; D011658:Pulmonary Fibrosis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins; D015820:Cadherins; D002135:Calcium-Binding Proteins; D003094:Collagen; D003849:Deoxyguanosine; D009538:Nicotine; C579666:FSP1 protein, rat; C498862:Acta2 protein, rat