Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene.
Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene.
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糖皮质激素抑制 UT-A 尿素转运蛋白基因的转录和表达。
DOI：
10.1152/ajprenal.00262.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Bagnasco,SerenaM
中科院分区：
文献类型：
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作者：
Peng,Tao;Sands,JeffM;Bagnasco,SerenaM
地塞米松治疗增加肾上腺切除大鼠内髓集合管（IMCD）的尿素排泄，降低尿素渗透性和尿素转运蛋白UT-A1蛋白丰度。我们研究了地塞米松治疗3天对大鼠肾髓质中几种UT-A mRNA转录物丰度的影响。通过北方印迹分析，与对照组相比，地塞米松处理大鼠的内髓质中UT-A1（71%）、UT-A3（75%）和UT-A3 b（75%）的mRNA表达显著降低，但UT-A2未降低。然后，我们使用表达糖皮质激素受体的LLC-PK 1-GR 101细胞测试了100 nM地塞米松对UT-A基因中启动子I活性的影响。地塞米松显著降低大鼠UT-A启动子I的活性（72%），但不影响UT-A启动子II。缺失分析和定点突变表明，-423和-244之间的序列对这种抑制作用很重要，而-363处的10 bp序列（在凝胶迁移试验中与核蛋白结合）对基础启动子活性是必需的。参与糖皮质激素抑制UT-A启动子I活性的具体因素仍有待确定。
Dexamethasone treatment increases urea excretion and decreases urea permeability and urea transporter UT-A1 protein abundance in the inner medullary collecting duct (IMCD) of adrenalectomized rats. We examined the effect of dexamethasone treatment for 3 days on the abundance of several UT-A mRNA transcripts in rat renal medulla. By Northern blot analysis, a significant decrease in mRNA expression was observed in the inner medulla of dexamethasone-treated rats compared with controls for UT-A1 (71%), UT-A3 (75%), and UT-A3b (75%), but not for UT-A2. We then tested the effect of 100 nM dexamethasone on the activity of promoter I in the UT-A gene, using LLC-PK1-GR101 cells that express the glucocorticoid receptor. Dexamethasone significantly decreased the activity of rat UT-A promoter I (72%) but did not affect UT-A promoter II. Deletion analysis and site-directed mutagenesis demonstrated that sequences between −423 and −244 are important for this inhibition and that a 10-bp sequence at −363, which binds a nuclear protein in a gel shift assay, is necessary for basal promoter activity. The specific factors involved in repression of UT-A promoter I activity by glucocorticoids remain to be determined.