Department of Medicine, Children's Hospital Boston, MA, USA.
J Am Soc Nephrol. 2011 Jun;22(6):1053-63. doi: 10.1681/ASN.2010080841. Epub 2011 May 5.
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, miR-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.
理解调节肾脏发育过程中肾祖细胞的机制应该有助于开发肾衰竭的治疗方法。microRNAs 通过对特定靶 mRNA 的转录后抑制来调节基因表达,有助于干细胞的分化,但它们在肾发生中的作用还不完全清楚。在这里,我们发现肾祖细胞中 microRNAs 的缺失会导致肾脏发育过程中这一群体过早耗尽。凋亡增加和促凋亡蛋白 Bim 的表达伴随着这种耗竭。在肾发生过程中 microRNA 表达的分析确定了几种在肾祖细胞中高表达的 microRNA(miR-10a、miR-106b、miR-17-5p),它们要么已知要么预测靶向 Bim。我们提出,microRNA 对凋亡的调节可能决定先天性肾单位的分配。此外,我们的数据表明促凋亡蛋白 Bim 是肾祖细胞中 microRNA 的靶标。