title: The pro-apoptotic protein Bim is a microRNA target in kidney progenitors.
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.
authors.affiliation: Department of Medicine, Children's Hospital Boston, MA, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ho
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pandey
authors.forename: Tobias
authors.initials: T
authors.lastname: Schatton
authors.forename: Sunder
authors.initials: S
authors.lastname: Sims-Lucas
authors.forename: Myda
authors.initials: M
authors.lastname: Khalid
authors.forename: Markus H
authors.initials: MH
authors.lastname: Frank
authors.forename: Sunny
authors.initials: S
authors.lastname: Hartwig
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Kreidberg
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D023421:Models, Animal; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; C543614:Mirn17 microRNA, mouse; D011518:Proto-Oncogene Proteins