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Träfflista för sökning "WFRF:(Kuruvilla L.) srt2:(2015-2019)"

Search: WFRF:(Kuruvilla L.) > (2015-2019)

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1.
  • Kraehling, J. R., et al. (author)
  • Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
  • 2016
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. © The Author(s) 2016.
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2.
  • Fleenor, Courtney J., et al. (author)
  • Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment
  • 2018
  • In: Molecular and Cellular Biology. - : AMER SOC MICROBIOLOGY. - 0270-7306 .- 1098-5549. ; 38:17
  • Journal article (peer-reviewed)abstract
    • Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Kruppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid cell development via a cell-extrinsic mechanism. Mice with inactivated Zfp521 genes (Zfp521(-/-)) possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. These results advance our understanding of ZFP521s role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies.
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