微小RNA (miRNAs)在肾脏生理调控中有重要的作用,而OREBP是目前唯一已知的一个可直接参与渗透应激调控的转录因子。在一篇最近发表于《核酸研究》的论文中，我们报道miR-200b和miR-717的下调与OREBP表达因应渗透应激的表达上调密切相关，首次揭示miRNA介导的基因沉默是肾细胞因应环境渗透压改变而调整OREBP基因表达的重要调控机制。然而，生物信息学分析显示，除了miR-200b和miR-717之外，还有多个来源于Sfbmt2 基因的 miRNA cluster成员可能在OREBP的转录后调控中有重要贡献。本项目因而建议以我们已经建立的miR-466a转基因小鼠模型为范例，深入研究Sfbmt2-cluster miRNAs在肾细胞中对渗透应激调控转录因子OREBP的调控作用。这些相关研究可望揭示OREBP表达调控、肾细胞和组织高渗应激调控以及尿液浓缩调控的新机制。

microRNAs (miRNAs) play important roles in physiological regulation in the kidney, whereas OREBP is the only known transcription factor involved in renal osmoregulation. In a recent paper by our lab, we reported that the down-regulation of miR-200b and miR-717 correlated with the up-regulation of OREBP under hypertonic condition, suggesting that miRNA-mediated gene silencing is an important regulatory mechanism for tonicity responsive regulation of OREBP expression. Bioinformatics analysis, however, suggested that in addition to miR-200b and miR-717, there is a large group of miRNAs derived from the 10th intron of the Sfmbt2 gene (Sfmbt2-cluster miRNAs) that might be involved in control of OREBP expression. In our current application, we propose to utilize the miR-466a (a member of the Sfmbt2-cluster miRNAs)transgenics as a paradigm to investigate the roles of Sfmbt2-cluster miRNAs in posttranscriptional regulation of OREBP, renal osmoregulation and urine concentrating mechanisms. This study is expected to yield important insights into regulations in renal function and diseases.