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path(MESH:"Porphyria, Erythropoietic")

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Entity

Name
Porphyria, Erythropoietic
Namespace
MeSH
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

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Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 33

a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Using isolated duodenal loops to measure the transepithelial iron transport, we found that CEP mice presented a higher rate of iron absorption than the WT mice, although the differences between the area under the curves did not reach statistical significance (Figure 3D). PubMed:28143953

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Cell Ontology (CL)
bone marrow cell
MeSH
Duodenum
MeSH
Porphyria, Erythropoietic
Text Location
Results

a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Serum iron was also increased in CEP mice, but this did not lead to elevated Tf saturation because Tf was also significantly increased, which is reminiscent of iron deficiency anemia and facilitates iron delivery to a larger number of erythroblasts (Table 1 and Figure 3G). PubMed:28143953

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Cell Ontology (CL)
bone marrow cell
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Iron was also detected in the macrophages of the red pulp of CEP mice, while almost no iron deposit was observed in the spleen of Hjv–/– mice (Figure 4B), confirming that Hb and “free” heme are the likely source of macrophage iron accumulation. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

As expected, Perl’s staining of CEP kidneys showed significant accumulation of iron in the renal cortical part, particularly in the proximal tubules (Figure 6A). PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

a(CHEBI:bilirubin) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

a(CHEBI:coproporphyrin) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Type I porphyrins (Uro and Copro) were increased in urine and feces (data not shown) and in RBCs of CEP mice (Table 1). PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Urine
Text Location
Results

a(CHEBI:uroporphyrin) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Type I porphyrins (Uro and Copro) were increased in urine and feces (data not shown) and in RBCs of CEP mice (Table 1). PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Urine
Text Location
Results

a(MESH:Erythroblasts) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Indeed, in this organ, there was a strong increase in the total number of erythroblasts at all stages of differentiation (Figure 2C). PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Spleen
MeSH
Porphyria, Erythropoietic
Text Location
Results

bp(GO:"apoptotic process") negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

However, in contrast to the bone marrow, there was no significant decrease between intermediate and late erythroblasts (Figure 2C) and we observed decreased rather than increased apoptosis, as usually observed in ineffective erythropoiesis22,23 (Figure 2D). PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Spleen
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Hpx) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

p(MGI:Hp) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

p(MGI:Hp) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

The Hp plasma concentration was very low in CEP mice (Figure 1A), probably because of an increased rate of its endocytosis and subsequent lysosomal degradation. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Slc40a1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

In addition, we observed an increase of ferroportin protein expression in duodenal enterocytes (Figure 3E and F). PubMed:28143953

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Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Duodenum
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Slc40a1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

In addition, despite an increase in ferritin expression, ferroportin expression was also induced in the liver of CEP mice (Figure 4E), suggesting an increase of iron release in the circulation to satisfy the high iron demand. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

act(p(INTERPRO:"Glucose-6-phosphate dehydrogenase")) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

These data suggest that erythrocytes surviving in the circulation are more resistant to in vitro hemolysis: they are likely to correspond to reticulocytes and could explain the increased G6PD activity in CEP erythrocytes (Table 1). PubMed:28143953

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Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(INTERPRO:"L-lactate dehydrogenase") positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

p(MGI:Bmp4) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

We thus analyzed BMP4 expression level in CEP mice and show its strong increase in the red pulp of the spleen (Figure 2E), likely contributing to the rapid formation of stress burst-forming unit erythroid progenitors (BFU-Es) as a consequence of the high levels of erythropoietin (Epo) in these mice (Table 1). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Spleen
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Cd163) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Interestingly, in both liver and spleen, the expression of the Hb-Hp receptor (CD163)29 was found to be fully suppressed at both the mRNA and protein levels (Figure 4C and D and Online Supplementary Figure S1B), suggesting a slowdown of Hb uptake in macrophages which may prevent excess iron overload. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Cubn) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Interestingly, in contrast with the preserved mRNA levels (data not shown), the immunostaining of the endocytic receptor megalin/cubilin complexes revealed evidence of increased cubilin protein expression (Figure 5B) with no significant changes in megalin protein abundance (data not shown). PubMed:28143953

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Ftl1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

As expected, serum ferritin was significantly increased in CEP mice (Figure 3H). PubMed:28143953

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Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Ftl1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Ferritin protein level was significantly increased in the cortex but not in the medulla of CEP mice, confirming exclusive iron handing in the proximal renal tubules in these mice (Figure 6B); no change in the mRNA-expression of ferritin was observed (Figure 6B). PubMed:28143953

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Hmox1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Moreover, HO-1 was highly expressed in the liver of CEP compared to WT mice (Figure 4E), confirming that residual heme uptake is rapidly degraded in the liver. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Slc11a2) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

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Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Tfrc) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

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Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Trf) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Serum iron was also increased in CEP mice, but this did not lead to elevated Tf saturation because Tf was also significantly increased, which is reminiscent of iron deficiency anemia and facilitates iron delivery to a larger number of erythroblasts (Table 1 and Figure 3G). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Cd163) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Interestingly, in both liver and spleen, the expression of the Hb-Hp receptor (CD163)29 was found to be fully suppressed at both the mRNA and protein levels (Figure 4C and D and Online Supplementary Figure S1B), suggesting a slowdown of Hb uptake in macrophages which may prevent excess iron overload. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Erfe) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Fam132b mRNA expression in bone marrow cells was significantly increased (30-fold compared to WT mice) (Figure 3C). PubMed:28143953

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Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Ftl1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Interestingly, the mRNA expression levels of HO-1 and ferroportin, which are both induced transcriptionally by free heme, were enhanced significantly in the cortex, but not in the medulla, of CEP mice, resulting in large increases in their protein abundance (Figure 6). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Hamp) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

As expected, hepcidin was markedly reduced, both in the liver (at the mRNA level) and in the serum (Figure 3A and B). PubMed:28143953

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Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Hmox1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Interestingly, the mRNA expression levels of HO-1 and ferroportin, which are both induced transcriptionally by free heme, were enhanced significantly in the cortex, but not in the medulla, of CEP mice, resulting in large increases in their protein abundance (Figure 6). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Lrp1) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

The mRNA level of CD91 was significantly reduced in the liver and was fully suppressed in the spleen (Online Supplementary Figure S1A and B). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Slc11a2) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

r(MGI:Tfrc) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

Out-Edges 33

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:uroporphyrin) View Subject | View Object

Type I porphyrins (Uro and Copro) were increased in urine and feces (data not shown) and in RBCs of CEP mice (Table 1). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Urine
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:coproporphyrin) View Subject | View Object

Type I porphyrins (Uro and Copro) were increased in urine and feces (data not shown) and in RBCs of CEP mice (Table 1). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Urine
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:bilirubin) View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(INTERPRO:"L-lactate dehydrogenase") View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Hpx) View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Hp) View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Hp) View Subject | View Object

The Hp plasma concentration was very low in CEP mice (Figure 1A), probably because of an increased rate of its endocytosis and subsequent lysosomal degradation. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation act(p(INTERPRO:"Glucose-6-phosphate dehydrogenase")) View Subject | View Object

These data suggest that erythrocytes surviving in the circulation are more resistant to in vitro hemolysis: they are likely to correspond to reticulocytes and could explain the increased G6PD activity in CEP erythrocytes (Table 1). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(MESH:Erythroblasts) View Subject | View Object

Indeed, in this organ, there was a strong increase in the total number of erythroblasts at all stages of differentiation (Figure 2C). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Spleen
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation bp(GO:"apoptotic process") View Subject | View Object

However, in contrast to the bone marrow, there was no significant decrease between intermediate and late erythroblasts (Figure 2C) and we observed decreased rather than increased apoptosis, as usually observed in ineffective erythropoiesis22,23 (Figure 2D). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Spleen
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Bmp4) View Subject | View Object

We thus analyzed BMP4 expression level in CEP mice and show its strong increase in the red pulp of the spleen (Figure 2E), likely contributing to the rapid formation of stress burst-forming unit erythroid progenitors (BFU-Es) as a consequence of the high levels of erythropoietin (Epo) in these mice (Table 1). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Spleen
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation r(MGI:Hamp) View Subject | View Object

As expected, hepcidin was markedly reduced, both in the liver (at the mRNA level) and in the serum (Figure 3A and B). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation r(MGI:Erfe) View Subject | View Object

Fam132b mRNA expression in bone marrow cells was significantly increased (30-fold compared to WT mice) (Figure 3C). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

Using isolated duodenal loops to measure the transepithelial iron transport, we found that CEP mice presented a higher rate of iron absorption than the WT mice, although the differences between the area under the curves did not reach statistical significance (Figure 3D). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Duodenum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

Serum iron was also increased in CEP mice, but this did not lead to elevated Tf saturation because Tf was also significantly increased, which is reminiscent of iron deficiency anemia and facilitates iron delivery to a larger number of erythroblasts (Table 1 and Figure 3G). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

Iron was also detected in the macrophages of the red pulp of CEP mice, while almost no iron deposit was observed in the spleen of Hjv–/– mice (Figure 4B), confirming that Hb and “free” heme are the likely source of macrophage iron accumulation. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

As expected, Perl’s staining of CEP kidneys showed significant accumulation of iron in the renal cortical part, particularly in the proximal tubules (Figure 6A). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

In addition, we observed an increase of ferroportin protein expression in duodenal enterocytes (Figure 3E and F). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Duodenum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

In addition, despite an increase in ferritin expression, ferroportin expression was also induced in the liver of CEP mice (Figure 4E), suggesting an increase of iron release in the circulation to satisfy the high iron demand. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Trf) View Subject | View Object

Serum iron was also increased in CEP mice, but this did not lead to elevated Tf saturation because Tf was also significantly increased, which is reminiscent of iron deficiency anemia and facilitates iron delivery to a larger number of erythroblasts (Table 1 and Figure 3G). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Ftl1) View Subject | View Object

As expected, serum ferritin was significantly increased in CEP mice (Figure 3H). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Ftl1) View Subject | View Object

Ferritin protein level was significantly increased in the cortex but not in the medulla of CEP mice, confirming exclusive iron handing in the proximal renal tubules in these mice (Figure 6B); no change in the mRNA-expression of ferritin was observed (Figure 6B). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation r(MGI:Cd163) View Subject | View Object

Interestingly, in both liver and spleen, the expression of the Hb-Hp receptor (CD163)29 was found to be fully suppressed at both the mRNA and protein levels (Figure 4C and D and Online Supplementary Figure S1B), suggesting a slowdown of Hb uptake in macrophages which may prevent excess iron overload. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Cd163) View Subject | View Object

Interestingly, in both liver and spleen, the expression of the Hb-Hp receptor (CD163)29 was found to be fully suppressed at both the mRNA and protein levels (Figure 4C and D and Online Supplementary Figure S1B), suggesting a slowdown of Hb uptake in macrophages which may prevent excess iron overload. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation r(MGI:Lrp1) View Subject | View Object

The mRNA level of CD91 was significantly reduced in the liver and was fully suppressed in the spleen (Online Supplementary Figure S1A and B). PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Hmox1) View Subject | View Object

Moreover, HO-1 was highly expressed in the liver of CEP compared to WT mice (Figure 4E), confirming that residual heme uptake is rapidly degraded in the liver. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Cubn) View Subject | View Object

Interestingly, in contrast with the preserved mRNA levels (data not shown), the immunostaining of the endocytic receptor megalin/cubilin complexes revealed evidence of increased cubilin protein expression (Figure 5B) with no significant changes in megalin protein abundance (data not shown). PubMed:28143953

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation r(MGI:Tfrc) View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

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Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation r(MGI:Slc11a2) View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Tfrc) View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Slc11a2) View Subject | View Object

However, the mRNA and protein expression of both TFR1 and DMT1 responsible for iron entry into renal cells were slightly decreased, although not reaching statistical significance (Online Supplementary Figure S4). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation r(MGI:Ftl1) View Subject | View Object

Interestingly, the mRNA expression levels of HO-1 and ferroportin, which are both induced transcriptionally by free heme, were enhanced significantly in the cortex, but not in the medulla, of CEP mice, resulting in large increases in their protein abundance (Figure 6). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation r(MGI:Hmox1) View Subject | View Object

Interestingly, the mRNA expression levels of HO-1 and ferroportin, which are both induced transcriptionally by free heme, were enhanced significantly in the cortex, but not in the medulla, of CEP mice, resulting in large increases in their protein abundance (Figure 6). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
inner renal cortex cell
MeSH
Kidney Cortex
MeSH
Porphyria, Erythropoietic
Text Location
Results

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.