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p(MGI:Tfeb)

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Entity

Name
Tfeb
Namespace
mgi
Namespace Version
20181021
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/mgi-names.belns

Appears in Networks 1

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading v1.0.0

In-Edges 3

a(MESH:Astrocytes) increases p(MGI:Tfeb) View Subject | View Object

Transcriptomic analysis of these isolated astrocytes revealed an increase in TFEB tran- scripts, as well as transcripts of several of its well-known target genes in the rTg4510 relative to wild-type controls PubMed:30108137

Appears in Networks:

path(MESH:Tauopathies) increases p(MGI:Tfeb) View Subject | View Object

In the rTg4510 mouse model of tauopathy (Ramsden et al., 2005; SantaCruz et al., 2005), gene set enrichment analysis (GSEA) of microarray data revealed a similar enrichment of TFEB’s tran- scriptional profile when comparing 4-mo-old transgenic mice with widespread NFTs to wild-type mice, indicating TFEB’s activation with tau pathology (Fig. 1 F). PubMed:30108137

Appears in Networks:

path(MESH:Tauopathies) increases p(MGI:Tfeb) View Subject | View Object

Examining the protein levels in another tauopathy mouse model, hippocampal lysates from PS19 mice (Yoshiyama et al., 2007) at 10 mo of age showed increases in TFEB and lysosomal proteins LAMP1 and CTSD com- pared with wild-type mice (Fig. S1, G and H). PubMed:30108137

Appears in Networks:

Out-Edges 20

p(MGI:Tfeb) hasVariant p(MGI:Tfeb, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(MGI:Tfeb) increases p(MGI:Lamp1) View Subject | View Object

as expected, the expression of several TFEB lysosomal target genes was signifi- cantly up-regulated in TFEB-transduced astrocytes, including lysosomal marker LAMP1 and lysosomal proteases, cathepsins A and B PubMed:30108137

Appears in Networks:

p(MGI:Tfeb) increases p(MGI:Ctsa) View Subject | View Object

as expected, the expression of several TFEB lysosomal target genes was signifi- cantly up-regulated in TFEB-transduced astrocytes, including lysosomal marker LAMP1 and lysosomal proteases, cathepsins A and B PubMed:30108137

Appears in Networks:

p(MGI:Tfeb) increases p(MGI:Ctsb) View Subject | View Object

as expected, the expression of several TFEB lysosomal target genes was signifi- cantly up-regulated in TFEB-transduced astrocytes, including lysosomal marker LAMP1 and lysosomal proteases, cathepsins A and B PubMed:30108137

Appears in Networks:

p(MGI:Tfeb) regulates act(a(MESH:Lysosomes)) View Subject | View Object

In sum, these results demonstrate that TFEB regulates the lysosomal pathway in primary astrocytes. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases act(a(MESH:Phagocytes)) View Subject | View Object

TFEB not only increased the proportion of cells taking up beads, but also increased the pro- portion of cells taking up multiple beads, suggesting an enhanced phagocytic capacity PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases a(HBP:"Tau fibrils") View Subject | View Object

Our results demonstrate a statistically significant increase of 12% in the uptake of pffs in TFEB transduced astrocytes relative to control at the 1-h time point, with a 22% relative increase in up- take in the TFEB transduced cells at 4 h PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases a(HBP:"Tau fibrils") View Subject | View Object

Flow cytometry revealed that Torin1 treatment of TFEB transduced astrocytes increased dye-conjugated pff uptake 63% relative to EGFP transduced controls as shown by median fluorescence in- tensity, while under basal conditions, the TFEB overexpressing astrocytes increased uptake just 18% relative to EGFP expressing controls (Fig. 2 K). Thus, TFEB enhances phagocytic pathways in astrocytes, in particular increasing the uptake of pffs. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases a(HBP:"Tau fibrils") View Subject | View Object

. Recapitulating the uptake assay with dye-conjugated pffs in TFEB KO astrocytes, we observed a modest reduction pff uptake compared with primary astrocytes from littermate controls PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases tloc(a(HBP:"Tau fibrils")) View Subject | View Object

In sum, these data suggest that TFEB stimulates uptake and trafficking of pffs to the lysosome for degradation. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases bp(MESH:Phagocytosis) View Subject | View Object

Flow cytometry revealed that Torin1 treatment of TFEB transduced astrocytes increased dye-conjugated pff uptake 63% relative to EGFP transduced controls as shown by median fluorescence in- tensity, while under basal conditions, the TFEB overexpressing astrocytes increased uptake just 18% relative to EGFP expressing controls (Fig. 2 K). Thus, TFEB enhances phagocytic pathways in astrocytes, in particular increasing the uptake of pffs. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases r(MGI:Lamp1) View Subject | View Object

qRT-PCR demonstrated undetectable transcript levels of TFEB as well as a reduction in LAMP1 mRNA in TFEB KO astrocytes compared with littermate controls PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases bp(MESH:Proteolysis) View Subject | View Object

Flow cytometry analysis of primary astrocytes incubated with DQ-BSA revealed an ∼60% increase in median fluorescence for TFEB-transduced astro- cytes, indicating that TFEB enhances uptake and proteolysis of DQ-BSA PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) causesNoChange p(MGI:Phf1) View Subject | View Object

Immunoblot- ting for total tau and phospho-tau antibodies, PHF1 and CP13, demonstrated no statistical difference in hippocampal brain ly- sate from TFEB- versus EGFP-injected rTg4510 male or female mice PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) decreases p(MGI:Mapt, pmod(Ph)) View Subject | View Object

Western blot a reduction in phospho-tau species recognized by AT8 (trending), AT180, and CP13 antibodies in the TFEB-injected mice PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) decreases p(MGI:Mapt, pmod(Ph)) View Subject | View Object

In the insoluble fraction, phospho- and total tau species were all reduced in the TFEB mice, as demonstrated by Western blot PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) causesNoChange p(MGI:Mapt, pmod(Ph)) View Subject | View Object

Quantifying the area fluorescence of MC1 staining for both hippocampi from sections representing the entire volume of hippocampus showed that astroglial TFEB had no impact on MC1 staining on the ipsi- lateral side, but significantly reduced the area of MC1 staining on the contralateral side PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
MeSH
Hippocampus

p(MGI:Tfeb) decreases p(MGI:Mapt) View Subject | View Object

In the insoluble fraction, phospho- and total tau species were all reduced in the TFEB mice, as demonstrated by Western blot PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) decreases path(MESH:Tauopathies) View Subject | View Object

Overall, these results show that astroglial TFEB overexpression reduces tau pathology and gliosis in the hippocampus of PS19 tauopathy mice. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
MeSH
Hippocampus

p(MGI:Tfeb) decreases path(MESH:Gliosis) View Subject | View Object

Overall, these results show that astroglial TFEB overexpression reduces tau pathology and gliosis in the hippocampus of PS19 tauopathy mice. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
MeSH
Hippocampus

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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.