Pulmonary elastin expression is decreased in the nitrofen-induced rat model of congenital diaphragmatic hernia.
OBJECTIVE
Babies with congenital diaphragmatic hernia (CDH) suffer from pulmonary hypoplasia and pulmonary hypertension. Elastin is a critical component of the extracellular matrix (EM) involved in pulmonary development and mechanics. Because CDH lungs are developmentally immature and have reduced compliance, the authors hypothesized that elastin deposition would be reduced and disorganized in the nitrofen rat model of CDH.


METHODS
Time-dated pregnant Sprague-Dawley rats were fed 100 mg of nitrofen on day 9 of gestation. Control rats did not receive nitrofen. The authors analyzed three groups of rats (n = 10 for each group): (1) control (C), (2) nitrofen no CDH (NC), and (3) nitrofen-induced CDH (CDH). On day 21.5 (term, 22 days), the fetuses were delivered by cesarean section, and the fetal lung was harvested. Elastin content, mRNA expression, and distribution were assessed with desmosine analysis, Northern blot analysis, and Hart's staining, respectively.


RESULTS
The mean desmosine content in picomole desmosine per milligram protein (pmD/mgP) +/- SD was 30 +/- 6.8 (C, n = 10), 25.1 +/- 10.1 (NC, n = 10), and 21.6 +/- 6.4 (CDH, n = 10). The comparison between CDH and controls was statistically significant (P =.026). Northern blot analysis showed decreased mRNA expression in the CDH sample. Hart's staining showed developmentally immature CDH lungs with less elastin deposition and disorganized distribution.


CONCLUSIONS
Pulmonary elastin expression is decreased and disorganized in the nitrofen-induced rat model of CDH. The decreased expression appears to be regulated at the level of transcription. Altered mechanical forces may be responsible for mediating the expression of elastin in CDH.
Mychaliska
George B
GB
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO, USA.
Officer
Susan M
SM
Heintz
Catherine K
CK
Starcher
Barry C
BC
Pierce
Richard A
RA
D000818:Animals; D003895:Desmosine / Q000378:metabolism*; D004195:Disease Models, Animal; D004549:Elastin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D010647:Phenyl Ethers; D011247:Pregnancy; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010647:Phenyl Ethers; D012333:RNA, Messenger; D003895:Desmosine; D004549:Elastin; C007350:nitrofen