Increased tropoelastin and procollagen expression in the lung of nitrofen-induced diaphragmatic hernia in rats.
OBJECTIVE
Collagen and elastin, the predominant components of the lung connective tissue network, have been suggested to have an important influence on lung compliance and maximal expansion. Decrease in lung compliance and distensibility often is seen in human congenital diaphragmatic hernia (CDH) lung as well as in experimentally produced CDH lung. The aim of this study was to investigate mRNA levels of tropoelastin and alpha1 (I) procollagen, the precursors of elastin, and type I collagen, respectively, in CDH lung and to determine whether antenatal dexamethasone treatment has any effect on the production of these extracellular matrix proteins.


METHODS
CDH model was induced in pregnant rats after administration of 100 mg nitrofen on day 9.5 of gestation (term, 22 days). Dexamethasone (0.25 mg/kg) was given on day 18.5 and 19.5. Cesarean section was performed on day 21. The fetuses were divided into three groups: group I, normal controls; group II, nitrofen-induced CDH; and group III, nitrofen-induced CDH with antenatal dexamethasone treatment. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate relative amounts of tropoelastin and alpha1 (I) procollagen mRNA.


RESULTS
Levels of both tropoelastin and alpha1 (I) procollagen mRNA were significantly increased in group II compared with group I (P< .05). Neither tropoelastin nor alpha1 (I) procollagen mRNA levels were significantly different between group II and III.


CONCLUSIONS
The increased local synthesis of tropoelastin and type I procollagen in CDH lung may be responsible for the increased rigidity and decreased compliance observed in the CDH hypoplastic lung. Glucocorticoids have no effect on pulmonary tropoelastin and alpha1 (I) procollagen gene expression in CDH lungs.
Taira
Y
Y
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Oue
T
T
Shima
H
H
Miyazaki
E
E
Puri
P
P
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000378:metabolism*; D065630:Hernias, Diaphragmatic, Congenital; D010647:Phenyl Ethers / Q000009:adverse effects; D011247:Pregnancy; D011347:Procollagen / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens; D014333:Tropoelastin / Q000378:metabolism*
D010647:Phenyl Ethers; D011347:Procollagen; D012333:RNA, Messenger; D013723:Teratogens; D014333:Tropoelastin; C007350:nitrofen