Differential regulation of SP-A1 and SP-A2 genes by cAMP, glucocorticoids, and insulin.
In the human fetal lung, surfactant protein A (SP-A) is encoded by two highly similar genes, SP-A1 and SP-A2, which are developmentally and hormonally regulated. Using primer extension analysis, we evaluated the levels of SP-A1 and SP-A2 mRNA transcripts in human fetal lung explants and in a human adult lung adenocarcinoma cell line (H441 cells) cultured in the absence or presence of either dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM), dexamethasone (10(-7) M), or insulin (2.5 micrograms/ml). In the human fetal lung explants, the content of SP-A1 mRNA was approximately four times that of SP-A2 mRNA. DBcAMP increased SP-A1 mRNA levels by 100% and SP-A2 mRNA levels by 500%, thus reducing the ratio of SP-A1 mRNA to SP-A2 mRNA to approximately 1:1. Dexamethasone inhibited all of the SP-A1 and SP-A2 mRNA transcripts to the same extent, by approximately 70%, whereas insulin inhibited all SP-A mRNA transcripts by approximately 60%. The ratio of SP-A1 to SP-A2 mRNA in dexamethasone- or insulin-treated explants was the same as the ratio observed in controls. In the H441 cells, SP-A1 mRNA levels were approximately 1.5 times that of SP-A2 mRNA levels. DBcAMP increased both SP-A1 and SP-A2 mRNA levels by 100%. Dexamethasone inhibited SP-A1 mRNA levels in the cell line by 60%, whereas SP-A2 mRNA levels were not significantly affected. Insulin inhibited SP-A1 mRNA levels in the cell line by 40% without affecting SP-A2 mRNA levels. These findings suggest that the two human SP-A genes are regulated differently in the two model systems.
Kumar
A R
AR
Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City 52242, USA.
Snyder
J M
JM
D000328:Adult; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000196:embryology / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D006023:Glycoproteins; D007328:Insulin; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D003994:Bucladesine; D003907:Dexamethasone; D000242:Cyclic AMP