Human SP-A1 and SP-A2 genes are differentially regulated during development and by cAMP and glucocorticoids

S. M. McCormick, C. R. Mendelson

Research output: Contribution to journalArticle

Abstract

Expression of the surfactant protein A (SP-A) gene is lung specific, developmentally induced, and regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoids. Humans have two highly similar genes encoding SP-A (SP-A1 and SP-A2). In the companion paper [S.M. McCormick, V. Boggaram, and C.R. Mendelson Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L354-L366, 1994] we report that SP-A1 and SP-A2 RNA transcripts are alternatively spliced at their 5' ends, resulting in nine different primer-extended transcripts. In the present study, primer extension was used to assess the relative levels of expression of the SP-A1 and SP-A2 genes in human adult lung tissue and in fetal lung tissues maintained in organ culture in the absence or presence of dibutyryl (DB)cAMP (1 mM) and dexamethasone (Dex, 10-7 M). Primer extension and Northern analysis were used to assess the effects of these agents on the levels of expression of these genes. In human adult lung tissue, 65% of the SP-A mRNA transcripts were derived from the SP-A2 gene, whereas only 35% were from SP-A1. On the other hand, in lung tissue from a 28-wk gestation neonate, only SP-A1 mRNA transcripts were detected, and, in midgestation fetal lung cultured in control medium, 65% of the SP-A mRNA was found to be SP-A1 and 35% was SP- A2. By contrast, when lung explants were incubated in the presence of DBcAMP, 67% of the SP-A mRNA transcripts were derived from the SP-A2 gene, and the remaining 33% were from SP-A1. In lung tissues treated with DBcAMP plus Dex, the ratio of SP-A2 to SP-A1 was shifted to a value similar to that observed in control tissues. Interestingly, DBcAMP caused an 11-fold increase in SP- A2 mRNA levels, whereas only a 2-fold induction by cAMP of SP-A1 mRNA levels was observed. Dex had little or no effect in reducing the levels of SP-A1 mRNA in DBcAMP-treated human fetal lung explants but caused a 90% reduction in the levels of SP-A2 mRNA. These findings suggest that the human SP-A2 gene is more responsive to the inductive effects of cAMP and the inhibitory effects of glucocorticoids than that encoding SP-A1.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume266
Issue number4 10-4
StatePublished - 1994

Fingerprint

varespladib methyl
Glucocorticoids
Pulmonary Surfactant-Associated Protein A
Lung
Bucladesine
Messenger RNA
Genes
Organ Culture Techniques
Cyclic AMP
Dexamethasone
Fetus
RNA
Gene Expression
Pregnancy

Keywords

  • adult lung
  • dexamethasone
  • dibutyryl adenosine 3',5'-cyclic monophosphate
  • fetal lung
  • messenger ribonucleic acid
  • Northern analysis
  • primer extension
  • surfactant protein A

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

@article{1ecad348b81d42cab9b903e78b0e6674,
title = "Human SP-A1 and SP-A2 genes are differentially regulated during development and by cAMP and glucocorticoids",
abstract = "Expression of the surfactant protein A (SP-A) gene is lung specific, developmentally induced, and regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoids. Humans have two highly similar genes encoding SP-A (SP-A1 and SP-A2). In the companion paper [S.M. McCormick, V. Boggaram, and C.R. Mendelson Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L354-L366, 1994] we report that SP-A1 and SP-A2 RNA transcripts are alternatively spliced at their 5' ends, resulting in nine different primer-extended transcripts. In the present study, primer extension was used to assess the relative levels of expression of the SP-A1 and SP-A2 genes in human adult lung tissue and in fetal lung tissues maintained in organ culture in the absence or presence of dibutyryl (DB)cAMP (1 mM) and dexamethasone (Dex, 10-7 M). Primer extension and Northern analysis were used to assess the effects of these agents on the levels of expression of these genes. In human adult lung tissue, 65{\%} of the SP-A mRNA transcripts were derived from the SP-A2 gene, whereas only 35{\%} were from SP-A1. On the other hand, in lung tissue from a 28-wk gestation neonate, only SP-A1 mRNA transcripts were detected, and, in midgestation fetal lung cultured in control medium, 65{\%} of the SP-A mRNA was found to be SP-A1 and 35{\%} was SP- A2. By contrast, when lung explants were incubated in the presence of DBcAMP, 67{\%} of the SP-A mRNA transcripts were derived from the SP-A2 gene, and the remaining 33{\%} were from SP-A1. In lung tissues treated with DBcAMP plus Dex, the ratio of SP-A2 to SP-A1 was shifted to a value similar to that observed in control tissues. Interestingly, DBcAMP caused an 11-fold increase in SP- A2 mRNA levels, whereas only a 2-fold induction by cAMP of SP-A1 mRNA levels was observed. Dex had little or no effect in reducing the levels of SP-A1 mRNA in DBcAMP-treated human fetal lung explants but caused a 90{\%} reduction in the levels of SP-A2 mRNA. These findings suggest that the human SP-A2 gene is more responsive to the inductive effects of cAMP and the inhibitory effects of glucocorticoids than that encoding SP-A1.",
keywords = "adult lung, dexamethasone, dibutyryl adenosine 3',5'-cyclic monophosphate, fetal lung, messenger ribonucleic acid, Northern analysis, primer extension, surfactant protein A",
author = "McCormick, {S. M.} and Mendelson, {C. R.}",
year = "1994",
language = "English (US)",
volume = "266",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 10-4",

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TY - JOUR

T1 - Human SP-A1 and SP-A2 genes are differentially regulated during development and by cAMP and glucocorticoids

AU - McCormick, S. M.

AU - Mendelson, C. R.

PY - 1994

Y1 - 1994

N2 - Expression of the surfactant protein A (SP-A) gene is lung specific, developmentally induced, and regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoids. Humans have two highly similar genes encoding SP-A (SP-A1 and SP-A2). In the companion paper [S.M. McCormick, V. Boggaram, and C.R. Mendelson Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L354-L366, 1994] we report that SP-A1 and SP-A2 RNA transcripts are alternatively spliced at their 5' ends, resulting in nine different primer-extended transcripts. In the present study, primer extension was used to assess the relative levels of expression of the SP-A1 and SP-A2 genes in human adult lung tissue and in fetal lung tissues maintained in organ culture in the absence or presence of dibutyryl (DB)cAMP (1 mM) and dexamethasone (Dex, 10-7 M). Primer extension and Northern analysis were used to assess the effects of these agents on the levels of expression of these genes. In human adult lung tissue, 65% of the SP-A mRNA transcripts were derived from the SP-A2 gene, whereas only 35% were from SP-A1. On the other hand, in lung tissue from a 28-wk gestation neonate, only SP-A1 mRNA transcripts were detected, and, in midgestation fetal lung cultured in control medium, 65% of the SP-A mRNA was found to be SP-A1 and 35% was SP- A2. By contrast, when lung explants were incubated in the presence of DBcAMP, 67% of the SP-A mRNA transcripts were derived from the SP-A2 gene, and the remaining 33% were from SP-A1. In lung tissues treated with DBcAMP plus Dex, the ratio of SP-A2 to SP-A1 was shifted to a value similar to that observed in control tissues. Interestingly, DBcAMP caused an 11-fold increase in SP- A2 mRNA levels, whereas only a 2-fold induction by cAMP of SP-A1 mRNA levels was observed. Dex had little or no effect in reducing the levels of SP-A1 mRNA in DBcAMP-treated human fetal lung explants but caused a 90% reduction in the levels of SP-A2 mRNA. These findings suggest that the human SP-A2 gene is more responsive to the inductive effects of cAMP and the inhibitory effects of glucocorticoids than that encoding SP-A1.

AB - Expression of the surfactant protein A (SP-A) gene is lung specific, developmentally induced, and regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoids. Humans have two highly similar genes encoding SP-A (SP-A1 and SP-A2). In the companion paper [S.M. McCormick, V. Boggaram, and C.R. Mendelson Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L354-L366, 1994] we report that SP-A1 and SP-A2 RNA transcripts are alternatively spliced at their 5' ends, resulting in nine different primer-extended transcripts. In the present study, primer extension was used to assess the relative levels of expression of the SP-A1 and SP-A2 genes in human adult lung tissue and in fetal lung tissues maintained in organ culture in the absence or presence of dibutyryl (DB)cAMP (1 mM) and dexamethasone (Dex, 10-7 M). Primer extension and Northern analysis were used to assess the effects of these agents on the levels of expression of these genes. In human adult lung tissue, 65% of the SP-A mRNA transcripts were derived from the SP-A2 gene, whereas only 35% were from SP-A1. On the other hand, in lung tissue from a 28-wk gestation neonate, only SP-A1 mRNA transcripts were detected, and, in midgestation fetal lung cultured in control medium, 65% of the SP-A mRNA was found to be SP-A1 and 35% was SP- A2. By contrast, when lung explants were incubated in the presence of DBcAMP, 67% of the SP-A mRNA transcripts were derived from the SP-A2 gene, and the remaining 33% were from SP-A1. In lung tissues treated with DBcAMP plus Dex, the ratio of SP-A2 to SP-A1 was shifted to a value similar to that observed in control tissues. Interestingly, DBcAMP caused an 11-fold increase in SP- A2 mRNA levels, whereas only a 2-fold induction by cAMP of SP-A1 mRNA levels was observed. Dex had little or no effect in reducing the levels of SP-A1 mRNA in DBcAMP-treated human fetal lung explants but caused a 90% reduction in the levels of SP-A2 mRNA. These findings suggest that the human SP-A2 gene is more responsive to the inductive effects of cAMP and the inhibitory effects of glucocorticoids than that encoding SP-A1.

KW - adult lung

KW - dexamethasone

KW - dibutyryl adenosine 3',5'-cyclic monophosphate

KW - fetal lung

KW - messenger ribonucleic acid

KW - Northern analysis

KW - primer extension

KW - surfactant protein A

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M3 - Article

VL - 266

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 10-4

ER -