The Pro-Apoptotic Protein Bim Is a MicroRNA Target in Kidney Progenitors

被引:80
作者
Ho, Jacqueline [2 ,3 ]
Pandey, Priyanka [2 ,3 ]
Schatton, Tobias [2 ,4 ,5 ]
Sims-Lucas, Sunder [6 ]
Khalid, Myda [2 ,3 ]
Frank, Markus H. [2 ,4 ,5 ]
Hartwig, Sunny [2 ,3 ]
Kreidberg, Jordan A. [1 ,2 ,3 ]
机构
[1] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Med,Div Nephrol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[3] Harvard Stem Cell Inst, Cambridge, MA USA
[4] Harvard Univ, Childrens Hosp Boston, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA
[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA
[6] Univ Pittsburgh, Sch Med, Dept Pediat, Div Nephrol, Pittsburgh, PA 15261 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2011年 / 22卷 / 06期
关键词
PROCESSING ENZYME DICER; POLYCYSTIC KIDNEY; BCL-2; DEFICIENCY; EXPRESSION; DIFFERENTIATION; DELETION; MORPHOGENESIS; FAMILY; LEADS; MICE;
D O I
10.1681/ASN.2010080841
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1053 / 1063
页数:11
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