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| Status |
Public on Nov 06, 2024 |
| Title |
Pseudohypoxia Due to PHD2 Deficiency Induces Endothelial Resistance to Apoptosis and Inflammation Independent of HIF2 alpha via AKT Activation and AIP1 Loss |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
PHD2 silencing activated AKT and ERK, inhibited JNK, and decreased AIP1, inhibiting apoptosis and proliferation and activating STAT. Like PHD2, AIP1 silencing affected the same kinase pathways and produced a similar dysfunctional endothelial cell phenotype, which was at least partially reversible with AKT inhibition. Transcriptomic profiling of human lung microvascular endothelial cells revealed that silencing PHD2 or AIP1 both induced an IFN/STAT-biased inflammatory signature with repression of E2F and MYC target genes. These in vitro results mirrored findings in lung vascular endothelial cells and tissues from PAH patients as well as rodent models of PAH.
PHD2 deficiency in human lung vascular endothelial cells induced an apoptosis-resistant, inflammatory, and hypo-proliferative phenotype. AKT activation and AIP1 loss, but not HIF signaling, drove these phenotypic aberrations.
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| Overall design |
Microarray analysis was conducted on samples from five independent experiments using LMVECs from the same donor at the same passage number to minimize variability. Cells were transfected with either scrambled pool non-targeting control siRNA, specific PHD2 (siPHD2, 15 nM), AIP1 (siAIP1, 15 nM), or both (siBoth) siRNA for 48 hours, and total RNA was then extracted using RNeasy miniprep kits (Qiagen).
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| Contributor(s) |
Wang S, Ferreyra GA, Demirkale CY, Awad KS, Chen L, Elinoff JM, Danner RL |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 12, 2023 |
| Last update date |
Nov 06, 2024 |
| Contact name |
Gabriela A Ferreyra |
| E-mail(s) |
[email protected]
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| Phone |
301-435-2317
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| Organization name |
Clinical Center
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| Department |
CCMD
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| Street address |
9000 Rockville Pike - Building 10 room 4D03
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA1051629 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE250030_RAW.tar |
23.3 Mb |
(http)(custom) |
TAR (of CEL) |
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