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PubMed: 24630724

Title
Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages.
Journal
Cell
Volume
156
Issue
None
Pages
1223-1234
Date
2014-03-13
Authors
Wang L | Wu X | Haldar M | Murphy KM | Arase H | Baltimore D | Briseño CG | Egawa T | Igarashi K | Kc W | Kohyama M | Kretzer NM | Murphy TL | Rajasekaran NS | Satpathy AT | So AY

Evidence 6f1f4e3e41
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Heme induced the expression of Ho1 and Blvrb as well as Slc40a1, which encodes the mammalian iron exporter (Figure 5A), in agreement with previous reports (Delaby et al., 2008).

a(CHEBI:heme) increases p(MGI:Hmox1) View Subject | View Object

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a(CHEBI:heme) increases p(MGI:Blvrb) View Subject | View Object

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a(CHEBI:heme) increases p(MGI:Slc40a1) View Subject | View Object

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Evidence 686f2e5aa3
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Heme-induced Spic expression was confirmed by reverse transcription PCR and was dose-dependent (Figure 2C).

a(CHEBI:heme) increases p(MGI:Spic) View Subject | View Object

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Evidence e15c6ca680
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In addition, Spic was induced as expected, as was Treml4, which can be used as a marker for RPM (Figure 5A).

a(CHEBI:heme) increases p(MGI:Spic) View Subject | View Object

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a(CHEBI:heme) increases p(MGI:Treml4) View Subject | View Object

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Evidence 14aee07328
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Heme has been suggested to induce polyubiquitination and proteasome-dependent degradation of BACH1 (Zenke-Kawasaki et al., 2007; Tan et al., 2013).

a(CHEBI:heme) positiveCorrelation deg(p(MGI:Bach1)) View Subject | View Object

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deg(p(MGI:Bach1)) positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Evidence 434336f8f2
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Here we showed that Bach1 was a transcriptional repressor of Spic and that heme-induced proteasome-dependent degradation of BACH1 protein in monocytes led to Spic expression and promoted RPM and BMM development (Figure 7F).

a(CHEBI:heme) positiveCorrelation deg(p(MGI:Bach1)) View Subject | View Object

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bp(HP:macrophage) positiveCorrelation p(MGI:Spic) View Subject | View Object

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Cell Ontology (CL)
splenic red pulp macrophage
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p(MGI:Bach1) decreases p(MGI:Spic) View Subject | View Object

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deg(p(MGI:Bach1)) increases p(MGI:Spic) View Subject | View Object

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deg(p(MGI:Bach1)) positiveCorrelation a(CHEBI:heme) View Subject | View Object

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p(MGI:Spic) positiveCorrelation bp(HP:macrophage) View Subject | View Object

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Cell Ontology (CL)
splenic red pulp macrophage
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Evidence 65d73ba82b
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CD169 expression was significantly decreased in Spic−/− BM indicating loss of these macrophages (Figure 1E).

g(MGI:Spic) positiveCorrelation p(MGI:Siglec1) View Subject | View Object

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p(MGI:Siglec1) positiveCorrelation g(MGI:Spic) View Subject | View Object

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Evidence e91c7bdce7
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Notably, heme mediated induction of SPIC-EGFP+ BMDM was significantly reduced with Bach1 overexpression suggesting that Bach1 may inhibit Spic expression (Figure 5C).

p(MGI:Bach1) decreases p(MGI:Spic) View Subject | View Object

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