The HIF target ATG9A is Essential for Epithelial Barrier Function and Tight Junction Biogenesis
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August 16, 2020

The HIF target ATG9A is Essential for Epithelial Barrier Function and Tight Junction Biogenesis

By Ben

intestinal epithelial cells (IECs) present in the metabolic state of low oxygen tension is called “physiological hypoxia.” An important factor in maintaining intestinal homeostasis is a transcription factor hypoxia-inducible factor (HIF), which is stabilized under hypoxic conditions and mediate the homeostatic response to low oxygen tension IEC.

To identify the target HIF transcription in IEC, chromatin immunoprecipitation (CHIP) is performed in Caco-2 IECs using HIF-1α or HIF-2α specific antibodies. CHIP-enriched DNA is hybridized to a promoter microarray custom (called CHIP-chip). Approach identified as containing autophagy as HIF-1 pathway in IEC main target. The binding of HIF-1 promoter ATG9A, only the transmembrane component in autophagy pathway, specifically enriched by exposure of IEC hypoxia.

This validation CHIP-chip revealed induction of ATG9A prominent, and tests promoter luciferase identified hypoxia response element functionally upstream of the TSS. hypoxia-mediated induction ATG9A lost in cells lacking HIF-1. Strikingly, we found that lentiviral-mediated knockdown ATG9A in IECs prevent epithelial barrier formation by> 95% and result in significant mislocalization of some tight junction (TJ) proteins.

Extensions of these findings suggest that ATG9A knockdown cells had intrinsic defects in the actin cytoskeleton, including mislocalization of TJ protein binding vasodilator-stimulated phosphoprotein (VASP). These results involve ATG9A as important to a few steps from the epithelial TJ biogenesis and actin cytoskeletal regulation. Our findings have a new application for a disorder involving epithelial barrier is compromised and suggest that targeting ATG9A may be a rational strategy for future therapeutic intervention.


paper reported one-step point-of-care testing (POCT) quantitative and sensitive chip built on the substrate patterned with microspots polydopamine perfluorinated arrays. Catching antibodies covalently move in microspots polydopamine, while the fluorescently labeled detection antibody is physically adsorbed on the surface of perfluorinated.

Chip POCT allowed one-step sandwich immunoassay and is able to directly detect analytes of whole blood without preprocessing sample. By taking further advantage of strong cooling fluorescence capabilities of polydopamine the free blocking substrate capable of achieving the same performance in detecting and measuring protein biomarker as a substrate with blocking treatment.

The HIF target ATG9A is Essential for Epithelial Barrier Function and Tight Junction Biogenesis
The HIF target ATG9A is Essential for Epithelial Barrier Function and Tight Junction Biogenesis

A new scoring system immunohistochemistry revealed the association of the C-terminal MET, ectodomain shedding and loss of E-cadherin with poor prognosis in oral squamous cell carcinoma

Using a tissue microarray showed that the C-terminal membrane immunoreactivity and MET ectodomain (ECD) shedding associated with poor prognosis in cancer of the mouth. Visible potential diagnostic value, extrapolation of these results to all parts of the network investigated.

Since MET orchestrates the epithelial to mesenchymal transition (EMT), the result refers to the loss of E-cadherin; readings for EMT known to be associated with a poor prognosis. MET C-terminal, N-terminal MET, and E-cadherin immunoreactivities checked on paraffin-embedded formalin-fixed sections 203 parallel oral cancer using the antibody clones D1C2, A2H2-3 and NCH-38.

p38
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Anti - p38-d
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E2220879 100ul
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Description: Available in various conjugation types.

p38 Mouse mAb
E2222580 100ul
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Description: Biotin-Conjugated, FITC-Conjugated , AF350 Conjugated , AF405M-Conjugated ,AF488-Conjugated, AF514-Conjugated ,AF532-Conjugated, AF555-Conjugated ,AF568-Conjugated , HRP-Conjugated, AF405S-Conjugated, AF405L-Conjugated , AF546-Conjugated, AF594-Conjugated , AF610-Conjugated, AF635-Conjugated , AF647-Conjugated , AF680-Conjugated , AF700-Conjugated , AF750-Conjugated , AF790-Conjugated , APC-Conjugated , PE-Conjugated , Cy3-Conjugated , Cy5-Conjugated , Cy5.5-Conjugated , Cy7-Conjugated Antibody

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E2340697 100ul
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Description: Available in various conjugation types.

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Description: Available in various conjugation types.

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E2381051 100ul
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Description: Available in various conjugation types.

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Description: Available in various conjugation types.

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p38 Rabbit pAb
E2251338 100ul
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Description: Available in various conjugation types.

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E2251719 100ul
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Description: Available in various conjugation types.

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MBS8540327-01mLAF635 0.1mL(AF635)
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anti-Crk p38
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EUR 400.8
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EUR 435.6
Description: Mouse polyclonal to Crk p38

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YF-PA11089 50 ug
EUR 435.6
Description: Mouse polyclonal to Crk p38

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YF-PA11090 100 ug
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7763-100 each
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p38 beta protein
30R-2875 5 ug
EUR 425
Description: Purified recombinant Human p38 beta protein

Inter- and intra-antibody relationship examined using the new scoring system, the distribution and the nonparametric median test. used survival analysis to examine the prognostic value immunoreactivities observed. The assessment of the three clones express the MET protein status (no, the feed, the C-terminal transmembrane positive), ECD shedding and EMT.

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