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Series GSE148987 Query DataSets for GSE148987
Status Public on Apr 18, 2023
Title The Mitochondrial Protein Mitofusin 2 Stabilizes Adherens Junctions and Suppresses Endothelial Inflammation via Modualtion of β-catenin Signaling
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Endothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of VE-cadherin as well as accessory proteins such as β-catenin and p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy (3D- SIM), we found that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and β-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/β-catenin complex disassociates from the AJs and translocates into the nucleus where Mfn2 negatively regulates the transcriptional activity of β-catenin. Endothelial-specific deletion of Mfn2 resulted in inflammatory injury, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non- canonical manner to suppress the inflammatory response by stabilizing cell-cell adherens junctions and by binding to the transcriptional activator β-catenin.
 
Overall design Total RNA was isolated by using phenol/chloroform and TRIzol Reagent, and its quality was evaluated with gel QC. Bulk RNA sequencing for 4 samples with 3 biological replicates each was performed with 3’ mRNA seq, 50 bp single end sequencing for coding genes at Core Genomic Facility in University of Illinois at Chicago. The sequenced reads from all samples were aligned to the human (hg38) reference genome with STAR v. 2.4.2, and the aligned reads were used to quantify mRNA expression by using HTSeq-count v. 0.6.1. Gene symbols were mapped to the ENSEMBL features using the biomaRt package v. 2.26.1.
 
Contributor(s) Rehman J, Kim Y, Jambusaria A
Citation(s) 33980844
Submission date Apr 20, 2020
Last update date Jul 18, 2023
Contact name Jalees Rehman
E-mail(s) jalees@uic.edu
Organization name UIC
Department Biochemistry and Molecular Genetics
Street address 909 S. Ashland Ave. MBRB 2072, Mailcode 669
City Chicago
State/province IL
ZIP/Postal code 60607
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM4486970 #1_shMfn2+DMSO
GSM4486971 #1_shMfn2+TNF
GSM4486972 #1_shMfn2+Dox
Relations
BioProject PRJNA626674
SRA SRP257579

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE148987_RAW.tar 9.0 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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