Pbx1 transcriptional regulation in renal vascular mural cells
Pbx1 transcriptional regulation in renal vascular mural cells
批准号:
9314809
负责人:
DORIS A HERZLINGER
金额:
$16.95万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-15 至 2019-08-31
关键词:
3-DimensionalAblationAdultAngiogenic FactorAnimalsAntibodiesArchitectureAttenuatedBindingBiological AssayBloodBlood VesselsBlood flowCell Differentiation processCell LineageCell Surface ProteinsCell physiologyCellsCessation of lifeCollaborationsContractile ProteinsDataDefectDevelopmentEnd stage renal failureEndotheliumEpithelialErythrocytesExhibitsFibrosisFrequenciesFunctional ImagingFunctional disorderGene DosageGenesGeneticGenetic TranscriptionGenotypeHomeostasisImageImaging TechniquesImmunofluorescence MicroscopyIn Situ HybridizationIn VitroInjuryKidneyKnockout MiceLabelMeasuresMediatingMicroscopicMicroscopyModelingMolecularMorphogenesisMusMutationNephronsPatternPericytesPhenocopyPhenotypePhysiologyPlayProcessPropertyProtocols documentationPublicationsPublishingRegional Blood FlowRegulationRenal Blood FlowRenal TissueRenal functionReporterRoleSemaphorin-3AShunt DeviceSignal PathwaySorting - Cell MovementStructureStructure of glomerular mesangiumTechniquesTestingTissue EngineeringTranscriptional RegulationTreesUreteral obstructionVascular Smooth MuscleVascularizationVenousVenous Malformationcontrast enhanceddesigndifferential expressionhemodynamicsin vivoinjuredkidney cortexkidney vascular structuremouse modelmulti-photonmutantnovelnovel therapeuticsoverexpressionprematureprogramsprotein expressionpupresearch studyresponseresponse to injurytranscription factortranscriptometranscriptome sequencingvascular bedvasoactive agent
中文摘要
总结
英文摘要
SUMMARY
Hemodynamic forces play a crucial role in renal physiology and pathophysiology but the cellular
and molecular mechanisms controlling the development of the specialized properties of the
renal vascular bed remain poorly understood. We recently discovered that the Foxd1 lineage,
which differentiates into pericytes, vascular smooth muscle, and the glomerular mesangium,
plays a fundamental role in this process. Specifically, conditional ablation of the TALE
transcription factor, Pbx1, in this lineage results in gross renal arterial patterning defects and
premature death of mutant pups. Strikingly, conditional Pbx1 ablation does not markedly
perturb renal epithelial morphogenesis. These data suggest that ablation of Pbx1 in the Foxd1
lineage reveals vascular patterning defects arising solely from the abnormal function of cells
derived from the Foxd1 lineage. Using murine genetics and state-of-the art functional imaging
techniques in collaboration with Dr. Peti-Peterdi, we will investigate the role of Pbx1
transcriptional regulation in the Foxd1 lineage. In Aim 1, we will determine how conditional Pbx1
ablation perturbs renal hemodynamics. Aim 2 will investigate the role of Pbx1-TR regulation in
controlling the secretion of angiogenic factors by Foxd1-derivatives. Finally, in Aim 3 we will test
whether Pbx1 transcriptional regulation in the mature kidney plays a role in its response to
injury. Results of these studies investigating the mechanisms of gross renal vascular patterning
will provide important clues for the design of protocols to functionally vascular renal tissues
engineered in vitro and may inspire novel techniques to attenuate renal fibrosis, a major cause
of end stage renal disease.
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依托单位:
FATE OF BF 2 EXPRESSING RENAL PROGENITORS
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资助金额:$32.01万
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财政年份:2001
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资助金额:$32.01万
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资助金额:$32.01万
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依托单位:
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依托单位:
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依托单位:
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海外基金