INSULIN REGULATION OF MESSENGER-RIBONUCLEIC-ACID FOR THE SURFACTANT-ASSOCIATED PROTEINS IN HUMAN FETAL LUNG INVITRO

被引:51
作者
DEKOWSKI, SA
SNYDER, JM
机构
[1] UNIV IOWA,COLL MED,DEPT ANAT,IOWA CITY,IA 52242
[2] UNIV IOWA,COLL MED,DEPT PEDIAT,IOWA CITY,IA 52242
关键词
D O I
10.1210/en.131.2.669
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Respiratory distress syndrome (RDS) is primarily caused by an immaturity in the synthesis and secretion of surfactant by the fetal lung type II cell. Fetal hyperinsulinemia associated with maternal diabetes places the newborn at an increased risk of developing RDS, and therefore, it ha been hypothesized that insulin inhibits type II cell differentiation. We have previously shown that insulin inhibits the accumulation of surfactant-associated protein A (SP-A), the major surfactant-associated protein, in human fetal lung explants maintained in vitro. In the present study, we used Northern blot analysis to evaluate the effects of insulin on the content of SP-A messenger RNA (mRNA) as well as on the content of mRNA for the hydrophobic surfactant-associated proteins SP-B and SP-C in human fetal lung explants maintained in vitro. Lung explants were maintained in serum-free medium with or without added insulin (0.25-2500 ng/ml) for up to 6 days. We observed that insulin, at concentrations of 25-2500 ng/ml, significantly inhibited the accumulation of SP-A mRNA when compared to controls (P < 0.01). The inhibitory effect of insulin on SP-A mRNA accumulation was dose dependent with an approximately 75% inhibition observed at 2500 ng/ml. Insulin, at the concentration of 2500 ng/ml, significantly inhibited the accumulation of SP-B mRNA by approximately 30% when compared to control levels (P < 0.01) but had no effect at lower concentrations. Insulin had no significant effect on SP-C mRNA levels at any concentration tested. Our findings provide evidence that insulin may delay fetal lung development by inhibiting SP-A and SP-B gene expression. A deficiency of these proteins in pulmonary surfactant may account for the increased incidence of RDS in infants of diabetic mothers.
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页码:669 / 676
页数:8
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