Developmental and hormonal regulation of surfactant protein C (SP-C) gene expression in fetal lung. Role of transcription and mRNA stability.

V Boggaram,R K Margana

doi:10.1016/s0021-9258(18)47052-4

Abstract

Pulmonary surfactant protein C (SP-C) gene expression is developmentally and hormonally regulated in fetal lung. In the present study, we investigated the role of transcriptional and posttranscriptional mechanisms in the developmental, cAMP, and dexamethasone induction of SP-C mRNA. We found that developmental induction of SP-C mRNA was not coincident with induction of SP-C gene transcription. SP-C mRNA levels reached approximately 90% of levels in adult lung on day 24 of gestation, whereas SP-C gene transcription was only approximately 4% of level in adult lung and did not increase until day 28 of gestation (term in rabbit = 31 days). Treatment of fetal lung tissues in vitro with dibutyryl cyclic AMP (Bt2cAMP) and dexamethasone increased SP-C mRNA accumulation by different mechanisms. Increase in SP-C mRNA accumulation by Bt2cAMP was the result of increased SP-C gene transcription, whereas increased SP-C mRNA accumulation by dexamethasone was due to stabilization of RNA. In control tissues the SP-C mRNA half-life (t1/2) was 11.2 h, and after dexamethasone treatment it increased to 30 h. These data show that both transcriptional and mRNA stabilization mechanisms regulate induction of SP-C gene expression during fetal lung development and by cAMP and dexamethasone in fetal lung in vitro.

Highlights

-90% of levelsinadultlungon day 24 of gestation, We previously isolated and characterizeSdP-C cDNAs in the whereas surfactant protein C (SP-C) gene transcription was onl-y4% of level in adult lung and did not increase until 2d8aoyf gestation
surfactant proteiAn (SP)-C gene expression during fetal lung development velopmentwere not coincident with increases in SP-C gene and byCAMP and dexamethasonein fetal lungin vitro. transcription; SP-C mRNAlevels reached 90% of levels found in adult lungby day 24of gestation but an increase SinP-C gene transcription was notfound until day 28 of gestation suggest
LA).We found a marked lag between the temporalinduction of SP-C genetranscription and elevation of SP-C mRNA levels

Summary

Introduction

-90% of levelsinadultlungon day 24 of gestation, We previously isolated and characterizeSdP-C cDNAs in the whereas SP-C gene transcription was onl-y4% of level in adult lung and did not increase until 2d8aoyf gestation (term in rabbit= 31 days). CAMPand Glucocorticoid Regulation of SP-C Gene Danscription andSP-C mRNALevels-In previous studies we found t h a t cyclic AMP analogs and dexamethasone increases the SP-C mRNA accumulation in 21-day fetal lung tissues in vitro in a time-dependent manner.

Results

Conclusion