XB-ART-54131
FASEB J
2017 Aug 01;318:3540-3554. doi: 10.1096/fj.201700010R.
Show Gene links
Show Anatomy links
Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development.
Cerqueira DM
,
Bodnar AJ
,
Phua YL
,
Freer R
,
Hemker SL
,
Walensky LD
,
Hukriede NA
,
Ho J
.
???displayArticle.abstract???
Low nephron endowment at birth has been associated with an increased risk for developing hypertension and chronic kidney disease. We demonstrated in an earlier study that conditional deletion of the microRNA (miRNA)-processing enzyme Dicer from nephron progenitors results in premature depletion of the progenitors and increased expression of the proapoptotic protein Bim (also known as Bcl-2L11). In this study, we generated a compound mouse model with conditional deletion of both Dicer and Bim, to determine the biologic significance of increased Bim expression in Dicer-deficient nephron progenitors. The loss of Bim partially restored the number of nephron progenitors and improved nephron formation. The number of progenitors undergoing apoptosis was significantly reduced in kidneys with loss of a single allele, or both alleles, of Bim compared to mutant kidneys. Furthermore, 2 miRNAs expressed in nephron progenitors (miR-17 and miR-106b) regulated Bim levels in vitro and in vivo Together, these data suggest that miRNA-mediated regulation of Bim controls nephron progenitor survival during nephrogenesis, as one potential means of regulating nephron endowment.-Cerqueira, D. M., Bodnar, A. J., Phua, Y. L., Freer, R., Hemker, S. L., Walensky, L. D., Hukriede, N. A., Ho, J. Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development.
???displayArticle.pubmedLink??? 28446592
???displayArticle.pmcLink??? PMC5503708
???displayArticle.link??? FASEB J
???displayArticle.grants??? [+]
P30 DK079307 NIDDK NIH HHS , R01 DK069403 NIDDK NIH HHS , R00 DK087922 NIDDK NIH HHS , K99 DK087922 NIDDK NIH HHS , T32 DK061296 NIDDK NIH HHS , R01 DK103776 NIDDK NIH HHS , R01 HD053287 NICHD NIH HHS
Species referenced: Xenopus laevis
Genes referenced: bcl2l11 dicer1 pax2 ret six2
References [+] :
Aerbajinai,
The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation.
2003, Pubmed
Aerbajinai, The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation. 2003, Pubmed
Akiyama, Bim-targeted cancer therapy: a link between drug action and underlying molecular changes. 2009, Pubmed
Barak, FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. 2012, Pubmed
Barreyro, Transcriptional regulation of Bim by FoxO3A mediates hepatocyte lipoapoptosis. 2007, Pubmed
Bartel, MicroRNAs: genomics, biogenesis, mechanism, and function. 2004, Pubmed
Barthson, Cytokines tumor necrosis factor-α and interferon-γ induce pancreatic β-cell apoptosis through STAT1-mediated Bim protein activation. 2011, Pubmed
Bernardo-Garcia, The transcription factor Glass links eye field specification with photoreceptor differentiation in Drosophila. 2016, Pubmed
Bertram, Why and how we determine nephron number. 2014, Pubmed
Biswas, Pro-apoptotic Bim induction in response to nerve growth factor deprivation requires simultaneous activation of three different death signaling pathways. 2007, Pubmed
Biswas, Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. 2007, Pubmed
Bonev, Methods to analyze microRNA expression and function during Xenopus development. 2012, Pubmed , Xenbase
Bouillet, Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. 1999, Pubmed
Bouillet, Degenerative disorders caused by Bcl-2 deficiency prevented by loss of its BH3-only antagonist Bim. 2001, Pubmed
Bouillet, Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim. 2001, Pubmed
Brenner, Glomeruli and blood pressure. Less of one, more the other? 1988, Pubmed
Brunjes, Developmental Markers Expressed in Neocortical Layers Are Differentially Exhibited in Olfactory Cortex. 2015, Pubmed
Brunskill, Microarrays and RNA-Seq identify molecular mechanisms driving the end of nephron production. 2011, Pubmed
Campone, c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1. 2011, Pubmed
Castoldi, A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). 2006, Pubmed
Castoldi, miChip: a microarray platform for expression profiling of microRNAs based on locked nucleic acid (LNA) oligonucleotide capture probes. 2007, Pubmed
Cebrian, The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment. 2014, Pubmed
Chen, Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan. 2015, Pubmed
Chen, Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity. 2007, Pubmed
Chi, Kif3a controls murine nephron number via GLI3 repressor, cell survival, and gene expression in a lineage-specific manner. 2013, Pubmed
Chu, Dicer function is required in the metanephric mesenchyme for early kidney development. 2014, Pubmed
Cullen-McEwen, Estimating total nephron number in the adult kidney using the physical disector/fractionator combination. 2012, Pubmed
Dijkers, Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. 2000, Pubmed
Dressler, Advances in early kidney specification, development and patterning. 2009, Pubmed
Dávila, Hsp27 binding to the 3'UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism. 2014, Pubmed
Eichhorn, Molecular analysis of functional redundancy among anti-apoptotic Bcl-2 proteins and its role in cancer cell survival. 2014, Pubmed
Essafi, Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells. 2005, Pubmed
Fuchs, Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation. 2012, Pubmed
Gebeshuber, Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1. 2013, Pubmed
Georgas, Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. 2009, Pubmed
Giam, BH3-only proteins and their roles in programmed cell death. 2008, Pubmed
Gilley, FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons. 2003, Pubmed
Gogada, Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer. 2013, Pubmed
Grieshammer, FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. 2005, Pubmed
Guo, Cardiomyocyte-specific role of miR-24 in promoting cell survival. 2015, Pubmed
Harada, Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia. 2012, Pubmed
Harfe, The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. 2005, Pubmed
Hartman, Cessation of renal morphogenesis in mice. 2007, Pubmed
Henderson-Smith, SMG1 identified as a regulator of Parkinson's disease-associated alpha-synuclein through siRNA screening. 2013, Pubmed
Hershko, Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis. 2004, Pubmed
Hinchliffe, Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. 1991, Pubmed
Ho, The pro-apoptotic protein Bim is a microRNA target in kidney progenitors. 2011, Pubmed
Hutcheson, Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity. 2008, Pubmed
Hübner, Multisite phosphorylation regulates Bim stability and apoptotic activity. 2008, Pubmed
Ingelfinger, Disparities in renal endowment: causes and consequences. 2008, Pubmed
Kamada, bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. 1995, Pubmed
Kan, The miR-106b-25 polycistron, activated by genomic amplification, functions as an oncogene by suppressing p21 and Bim. 2009, Pubmed
Katz, Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells. 2014, Pubmed
Kobayashi, Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. 2008, Pubmed
Kreidberg, WT-1 is required for early kidney development. 1993, Pubmed
Köhler, Activated Nrf2 impairs liver regeneration in mice by activation of genes involved in cell-cycle control and apoptosis. 2014, Pubmed
LaBelle, A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. 2012, Pubmed
Lechner, The molecular basis of embryonic kidney development. 1997, Pubmed
Lei, JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. 2003, Pubmed
Leon, BimEL as a possible molecular link between proteasome dysfunction and cell death induced by mutant huntingtin. 2010, Pubmed
Ley, Regulatory phosphorylation of Bim: sorting out the ERK from the JNK. 2005, Pubmed
Liu, The miR-24-Bim pathway promotes tumor growth and angiogenesis in pancreatic carcinoma. 2015, Pubmed
Livak, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. 2001, Pubmed
Lu, p38-MAP kinase activation followed by BIM induction is essential for glucocorticoid-induced apoptosis in lymphoblastic leukemia cells. 2006, Pubmed
Luyckx, The clinical importance of nephron mass. 2010, Pubmed
Mao, The metastasis suppressor, N-myc downregulated gene 1 (NDRG1), is a prognostic biomarker for human colorectal cancer. 2013, Pubmed
Marrone, MicroRNA-17~92 is required for nephrogenesis and renal function. 2014, Pubmed
Matsui, Cytokines direct the regulation of Bim mRNA stability by heat-shock cognate protein 70. 2007, Pubmed
Montagne, Sara endosomes and the asymmetric division of intestinal stem cells. 2014, Pubmed
Nagalakshmi, Dicer regulates the development of nephrogenic and ureteric compartments in the mammalian kidney. 2011, Pubmed
Nakayama, Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. 1994, Pubmed
Neves, Jagged 1 regulates the restriction of Sox2 expression in the developing chicken inner ear: a mechanism for sensory organ specification. 2011, Pubmed
Nishinakamura, Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. 2001, Pubmed
Perantoni, Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. 2005, Pubmed
Perier, Mitochondrial biology and Parkinson's disease. 2012, Pubmed
Poladia, Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. 2006, Pubmed
Puthalakath, ER stress triggers apoptosis by activating BH3-only protein Bim. 2007, Pubmed
Qian, miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes. 2011, Pubmed
Quinlan, A common variant of the PAX2 gene is associated with reduced newborn kidney size. 2007, Pubmed
Ren, BH3-only molecule Bim mediates β-cell death in IRS2 deficiency. 2014, Pubmed
Ridinger-Saison, Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia. 2013, Pubmed
Romaker, MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney. 2014, Pubmed , Xenbase
Rothenpieler, Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development. 1993, Pubmed
Rumballe, Nephron formation adopts a novel spatial topology at cessation of nephrogenesis. 2011, Pubmed
Sanphui, FoxO3a is activated and executes neuron death via Bim in response to β-amyloid. 2013, Pubmed
Saxén, Early organogenesis of the kidney. 1987, Pubmed
Schuchardt, Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development. 1996, Pubmed
Self, Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. 2006, Pubmed
Sims-Lucas, Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development. 2011, Pubmed
Sionov, Regulation of Bim in Health and Disease. 2015, Pubmed
Sorenson, Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. 1995, Pubmed
Strasser, The role of BH3-only proteins in the immune system. 2005, Pubmed
Sunters, FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines. 2003, Pubmed
Takasato, Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. 2014, Pubmed
Takeuchi, Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease. 2005, Pubmed
Ventura, Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. 2008, Pubmed
Wali, The proapoptotic BH3-only proteins Bim and Puma are downstream of endoplasmic reticulum and mitochondrial oxidative stress in pancreatic islets in response to glucotoxicity. 2014, Pubmed
Wang, miR-24 regulates intrinsic apoptosis pathway in mouse cardiomyocytes. 2014, Pubmed
Weber, SIX2 and BMP4 mutations associate with anomalous kidney development. 2008, Pubmed
Wilczynska, The complexity of miRNA-mediated repression. 2015, Pubmed
Xiao, Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. 2008, Pubmed
Xiao, Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy. 2016, Pubmed
Yang, Acetylation of FoxO1 activates Bim expression to induce apoptosis in response to histone deacetylase inhibitor depsipeptide treatment. 2009, Pubmed
Zhang, A common RET variant is associated with reduced newborn kidney size and function. 2008, Pubmed
Zhang, The pro-apoptotic protein Bim is a convergence point for cAMP/protein kinase A- and glucocorticoid-promoted apoptosis of lymphoid cells. 2004, Pubmed
Zhong, Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25. 2012, Pubmed