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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
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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.
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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.
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Contributor(s) |
Rehman J, Kim Y, Jambusaria A |
Citation(s) |
33980844 |
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Submission date |
Apr 20, 2020 |
Last update date |
Jul 18, 2023 |
Contact name |
Jalees Rehman |
E-mail(s) |
jalees@uic.edu
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Organization name |
UIC
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Department |
Biochemistry and Molecular Genetics
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Street address |
909 S. Ashland Ave. MBRB 2072, Mailcode 669
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City |
Chicago |
State/province |
IL |
ZIP/Postal code |
60607 |
Country |
USA |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (12)
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Relations |
BioProject |
PRJNA626674 |
SRA |
SRP257579 |