Human SP-A 3'-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone.
Human surfactant protein A (SP-A) is encoded by two genes (SP-A1, SP-A2), and each is identified with several alleles. SP-A is involved in normal lung function, innate immunity, inflammatory processes, and is regulated by glucocorticoids. We investigated the role of 3'-untranslated region (UTR) of 10 SP-A variants on gene expression using transient transfection of 3'-UTR constructs in the human lung adenocarcinoma cell line NCI-H441. We found: 1) both basal mRNA and protein levels of the reporter gene of SP-A 3'-UTR constructs are significantly (P < 0.01) reduced compared with controls (vector pGL3 and surfactant protein B pGL3) and that differences exist among alleles; and 2) after dexamethasone (Dex) treatment (100 nM for 16 h), mRNA was reduced (31-51%). Seven alleles showed a significant decrease (P < 0.05) in mRNA, and three did not. Reporter activity was also decreased, from 17% (1A(1)) to 38% (1A), with six alleles showing a significant decrease. The data indicate that the 3'-UTR of SP-As play a differential role in SP-A basal expression and in response to Dex. Therefore, a careful consideration of individual use of steroid treatment may be considered.
Wang
Guirong
G
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Guo
Xiaoxuan
X
Floros
Joanna
J
D020413:3' Untranslated Regions / Q000235:genetics; D000230:Adenocarcinoma; D000483:Alleles; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D020413:3' Untranslated Regions; D005938:Glucocorticoids; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; D003907:Dexamethasone; D008156:Luciferases