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Series GSE250030 Query DataSets for GSE250030
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
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.
 
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).
 
Contributor(s) Wang S, Ferreyra GA, Demirkale CY, Awad KS, Chen L, Elinoff JM, Danner RL
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Submission date Dec 12, 2023
Last update date Nov 06, 2024
Contact name Gabriela A Ferreyra
E-mail(s) gferreyra@cc.nih.gov
Phone 301-435-2317
Organization name Clinical Center
Department CCMD
Street address 9000 Rockville Pike - Building 10 room 4D03
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL23159 [Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay)
Samples (20)
GSM7971595 siControl_1
GSM7971596 siPHD2_1
GSM7971597 siAIP1_1
Relations
BioProject PRJNA1051629

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Supplementary file Size Download File type/resource
GSE250030_RAW.tar 23.3 Mb (http)(custom) TAR (of CEL)

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