Human SP-A 3′-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone
Human SP-A 3′-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone
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DOI：
10.1152/ajplung.00375.2002
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发表时间：
2003-05-01
影响因子：
4.9
通讯作者：
Floros, J
中科院分区：
文献类型：
--
作者：
Wang, GR;Guo, XX;Floros, J
人表面活性蛋白A(SP-A)由两个基因(SP-A1、SP-A2)编码，每个基因都含有多个等位基因。SP-A参与正常肺功能、先天免疫、炎症过程，并受糖皮质激素调节。我们通过瞬时转染人肺腺癌细胞株NCI-H441，研究了10个SP-A变异体的3‘-非翻译区对基因表达的影响。我们发现：1)SP-A 3‘-UTR报告基因的基础mRNA和蛋白水平均显著低于对照组(载体pGL3和表面活性蛋白B pGL3)，且存在等位基因差异；地塞米松(Dex)处理(100 nM，16h)后，其mRNA水平降低(31-51%)。7个等位基因的mRNA表达显著降低(P<0.05)，3个等位基因的表达没有显著降低。报告活性也下降，从17%(1A(1))降至38%(1A)，6个等位基因显著下降。这些数据表明，SP-AS的3‘-UTR在SP-A的基础表达和对Dex的反应中起着不同的作用。因此，可以考虑仔细考虑个体化使用类固醇治疗。
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.