| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Research Abstract |
Purpose Both the mortality and morbidity associated with congenital diaphragmatic hernia(CDH) are mainly caused by pulmonary hypoplasia and persistent pulmonary hypertension. A previous study revealed that insulin-like growth factors(IGFs) play important roles in fetal lung development. The aim of this study was to investigate the effect of IGF-1 and IGF-2 on tissue cultures of fetal hypoplastic lungs obtained from nitrofen-induced CDH model rats.Methods Pregnant rats were exposed to nitrofen on day 9 of gestation(D9). Fetuses were harvested on D18 by caesarian section. Lung specimens of the CDH(+) fetus were divided into three groups ; control, IGF-1, and IGF-2. The specimens from the control group were cultured in culture medium without IGFs. The IGF-1 group specimens were cultured with IGF-1(500 ng/ml), and those in the IGF-2 group were cultured with IGF-2(500 ng/ml). The mRNA expression of TTF-1, T1a and a-SMA were analyzed in each group using real-time RT-PCR after 24 and 48 h of
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incubation. Immunohistochemical staining of these markers was also assessed for each of the cultured specimens. Results There was a significant increase in the expression of both TTF-1 and T1a mRNA in the IGF-2 group, in comparison to the control group after 48 h of culture. Immunohistochemical
Methods Pregnant rats were exposed to nitrofen on day 9 of gestation(D9). Fetuses were harvested on D18 by caesarian section. Lung specimens of the CDH(+) fetus were divided into three groups ; control, IGF-1, and IGF-2. The specimens from the control group were cultured in culture medium without IGFs. The IGF-1 group specimens were cultured with IGF-1(500 ng/ml), and those in the IGF-2 group were cultured with IGF-2(500 ng/ml). The mRNA expression of TTF-1, T1a and a-SMA were analyzed in each group using real-time RT-PCR after 24 and 48 h of incubation. Immunohistochemical staining of these markers was also assessed for each of the cultured specimens.
Results There was a significant increase in the expression of both TTF-1 and T1a mRNA in the IGF-2 group, in comparison to the control group after 48 h of culture. Immunohistochemicalstaining revealed that the cell morphology was changed from cuboidal to squamous type in the IGF-2 group.
Conclusions An increased mRNA expression of the markers related to type 1 and 2 alveolar epithelial cells, and morphological changes in the epithelial cells were observed in the IGF-2 group. The administration of IGF-2 to nitrofen-induced hypoplastic lungs might lead to alveolar maturation, which thus results in their improved development. Less
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