The pro-apoptotic protein Bim is a microRNA target in kidney progenitors

J Am Soc Nephrol. 2011 Jun;22(6):1053-63. doi: 10.1681/ASN.2010080841. Epub 2011 May 5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology*
  • Bcl-2-Like Protein 11
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Kidney / cytology
  • Kidney / embryology*
  • Kidney / physiology*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • MicroRNAs / physiology*
  • Models, Animal
  • Pregnancy
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Stem Cells / cytology
  • Stem Cells / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Membrane Proteins
  • MicroRNAs
  • Mirn106 microRNA, mouse
  • Mirn17 microRNA, mouse
  • Proto-Oncogene Proteins