Human SP-A1 and SP-A2 genes are differentially regulated during development and by cAMP and glucocorticoids.
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(-4) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
McCormick
S M
SM
Department of Biochemistry, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Mendelson
C R
CR
D000328:Adult; D000375:Aging / Q000502:physiology*; D001483:Base Sequence; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000502:physiology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*
D005938:Glucocorticoids; D015335:Molecular Probes; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D003994:Bucladesine; D003907:Dexamethasone; D000242:Cyclic AMP