醛固酮调控WNK4基因表达及其机制的研究  

Expression of WNK4 gene regulated by aldosterone

作　　者：由田[1] 赵妍[2] 邱广斌[3] 

机构地区：[1]中国医科大学第一临床学院急诊科,沈阳110001 [2]沈阳市妇婴医院遗传科 [3]解放军第202医院检验科

出　　处：《中华医学遗传学杂志》2013年第3期297-300,共4页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（30500293）

摘　　要：目的研究醛固酮调控WNK4基因表达情况及其作用机制。方法以正常饮食饮水的大鼠为对照组，实验组3组大鼠分别以醛固酮注射1d、3d及高钾饮食诱导大鼠内源醛固酮增高，检测大鼠血清醛固酮水平及血清和24h尿液中K＋、Na＋和Cl-水平，用实时荧光定量PCR检测大鼠肾脏组织WNK4表达，转染WNK4启动子区荧光素酶报告基因载体pGL3-WNK4—484和pGL3-WNK4—275至肾源细胞系HEK239细胞中，醛固酮刺激24h后用双荧光素酶报告系统检测荧光素酶活性的变化。结果实验组较对照组大鼠血清醛固酮水平均升高，尿液K＋浓度均升高，尿液Na＋。浓度均降低，差异有统计学意义，高钾组大鼠尿液中Cl-显著升高；实验组大鼠血清K＋、Na＋和Cl-浓度均无明显变化。实验组大鼠肾脏组织中WNK4表达明显下降。在醛固酮刺激下，pGL3-WNK4—484质粒的荧光素酶活性下降了3．5倍，pGL3一WNK4—275质粒的荧光素酶活性无明显变化。结论醛固酮可作用于WNK4基因上游的糖皮质激素反应元件上，发挥其下调基因表达的作用。Objective To study the expression and mechanism of WNK4 gene regulated by aldosterone. Methods Wistar rats were treated with aldosterone and potassium water. Serum aldosterone and ion as well as urine ion were measured. The expression of WNK4 gene in kidney tissues was detected by real-time PCR. Kidney-derived HEK293 cells were cultured, transfected with pGL3-WNK4, and then stimulated by aldosterone. After 24 h of transfection, lueiferase activities of the plasmid were detected. Results Compared with those of the controls, serum aldosterone and urine K＋ of experimental rats were significantly elevated, whilst urine Na＋ was significantly decreased. And urine Cl- was significantly increased only in the group of high K＋. Serum K＋, Na＋ and Cl- showed no significant difference. Expression of WNK4 gene in kidney tissues was significantly decreased. The luciferase activity of pGL3- WNK4-484 plasmid has decreased after stimulated with aldosterone, while the activity of pGL3-WNK4-275 showed no change. Conclusion Aldosterone can down-regulate the expression of WNK4 through binding with regulatory element in the upstream of the gene.

关 键 词：WNK4基因 醛固酮 糖皮质激素反应元件 

分 类 号：R341[医药卫生—基础医学]