Effects of Antenatal Administration of Keratinocyte Growth Factor (KGF), Epidermal Growth Factor (EGF), and Dexamethasone on mRNA Levels of Surfactant Proteins in Fetal Mouse Lungs

ABSTRACT

PURPOSE: Growth factors such as keratinocyte growth factor (KGF) and epidermal growth factor (EGF) have been shown to stimulate alveolar proliferation and pulmonary surfactant production in neonatal animals, raising the question of their antenatal uses. We studied the effects of antenatal administration of recombinant human KGF (rhKGF), recombinant human EGF (rhEGF), or dexamethasone (Dexa) in mouse pups on mRNA synthesis of surfactant proteins A, B, and C. METHODS: Time-dated pregnant mice were divided into 5 groups. At gestational day 16, the pregnant mice received intraperitoneal injection of saline, rhKGF, rhKGF+Dexa, Dexa alone, or rhEGF. Fetuses were delivered by cesarean section 24 h later. Lung tissues were obtained for isolation of RNA and realtime RT-PCR for SP-A, -B, and -C. RESULTS: Relative SP-A mRNA levels of any of the treatment groups were not significantly different from the control group. Either KGF or Dexa group did not show higher levels of SP-B mRNA than control group. Relative mean values of SP-B mRNA of KGF+Dexa and EGF groups were higher than the control group, but not statistically significant. Even though there was a trend of increasing levels of SP-C mRNA in all the treatment groups, the differences were not statistically significant. CONCLUSION: Antenatal intraperitoneal administration of KGF, EGF, or dexamethasone to pregnant mice did not increase the mRNA expressions of surfactant proteins in preterm mouse pups. However, the effects of different doses, timing, and routes of administration are important factors that may influence the outcomes and should further be investigated in the future.