4.7 Article

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

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JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 22, 期 6, 页码 1053-1063

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AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2010080841

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资金

  1. National Institutes of Diabetes and Digestive and Kidney Diseases
  2. Harvard Stem Cell Institute
  3. Kidney Research Scientist Core Education and National Training Program (KRESCENT)
  4. March of Dimes, Pediatric Chairs of Canada
  5. SickKids Foundation
  6. American Heart Association Founders Affiliate
  7. Rodent Histopathology Core Facility of the Dana-Farber/Harvard Cancer [NIH-P30-CA-06516]

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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.

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