The Pro-Apoptotic Protein Bim Is a MicroRNA Target in Kidney Progenitors
The Pro-Apoptotic Protein Bim Is a MicroRNA Target in Kidney Progenitors
复制标题
DOI：
10.1681/asn.2010080841
复制
发表时间：
2011-06-01
影响因子：
13.6
通讯作者：
Kreidberg, Jordan A.
中科院分区：
文献类型：
--
作者：
Ho, Jacqueline;Pandey, Priyanka;Kreidberg, Jordan A.
了解肾脏发育过程中调节肾单位祖细胞的机制应有助于肾衰竭治疗方法的开发。微小核糖核酸（MicroRNAs）通过对特定靶信使核糖核酸（mRNAs）的转录后抑制来调节基因表达，有助于干细胞的分化，但其在肾发生中的作用尚未完全清楚。在此，我们发现在肾单位祖细胞中微小核糖核酸的缺失会导致肾脏发育过程中该细胞群过早耗竭。细胞凋亡增加以及促凋亡蛋白Bim的表达伴随这种耗竭出现。对肾发生过程中微小核糖核酸表达的分析鉴定出在肾单位祖细胞中几种高度表达的微小核糖核酸（miR - 10a、miR - 106b、miR - 17 - 5p），它们已知或被预测可靶向Bim。我们提出微小核糖核酸对细胞凋亡的调节可能决定先天性肾单位数量。此外，我们的数据表明促凋亡蛋白Bim是肾单位祖细胞中的一个微小核糖核酸作用靶点。
Understanding the mechanisms that regulate nephron progenitors during kidney development should aid development of therapies for renal failure. MicroRNAs, which modulate gene expression through post-transcriptional repression of specific target mRNAs, contribute to the differentiation of stem cells, but their role in nephrogenesis is incompletely understood. Here, we found that the loss of miRNAs in nephron progenitors results in a premature depletion of this population during kidney development. Increased apoptosis and expression of the pro-apoptotic protein Bim accompanied this depletion. Profiling of miRNA expression during nephrogenesis identified several highly expressed miRNAs (miR-10a, nniR-106b, miR-17-5p) in nephron progenitors that are either known or predicted to target Bim. We propose that modulation of apoptosis by miRNAs may determine congenital nephron endowment. Furthermore, our data implicate the pro-apoptotic protein Bim as a miRNA target in nephron progenitors.