Regulation of WNK1 Expression by miR-192 and Aldosterone
Regulation of WNK1 Expression by miR-192 and Aldosterone
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DOI：
10.1681/asn.2009111186
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发表时间：
2010-10-01
影响因子：
13.6
通讯作者：
Jeunemaitre, Xavier
中科院分区：
文献类型：
--
作者：
Elvira-Matelot, Emilie;Zhou, Xiao-ou;Jeunemaitre, Xavier
WNK1和WNK4编码WNK丝氨酸-苏氨酸激酶亚家族的两个成员。WNK1表达越高，血压越高。启动子、增强子、抑制子和绝缘子的组合调节WNK1的表达，但microrna是否也调节WNK1的表达尚不清楚。在这里，计算分析显示miR-192和miR-215的靶序列存在于普遍存在的L-和肾脏特异性KS-WNK1的3 '非翻译区域的同一位点。我们通过瞬时转染和报告基因试验对这一目标序列进行了功能性验证。尽管我们观察到这两种mir沿远端肾元表达，但只有miR-192在体外调节内源性WNK1。此外，钾负荷、钠消耗和醛固酮输注均显著降低了miR-192在肾脏中的表达。综上所述，这些结果表明mir -驱动的醛固酮基因调控机制以及miR-192在调节肾脏钠钾平衡中的作用。
WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown. Here, computational analysis revealed the presence of a target sequence for miR-192 and miR-215 at the same site in the 3 ' untranslated region of the ubiquitous L- and the kidney-specific KS-WNK1. We functionally validated this target sequence by transient transfection and reporter assays. Although we observed expression of both miRs along the distal nephron, only miR-192 regulated endogenous WNK1 ex vivo. Furthermore, a potassium load, sodium depletion, and aldosterone infusion each significantly reduced miR-192 expression in the kidney. Taken together, these results suggest a miR-driven mechanism of gene regulation by aldosterone and a role for miR-192 in the regulation of sodium and potassium balance in the kidney.