 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Mar 07, 2019 |
| Title |
Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We aimed to understand the role of cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT) in the immunosuppressive phase of lipopolysaccharide (LPS)-induced endotoxic shock. The liver plays an important role in immunity and organ dysfunction; therefore, on liver RNA sequencing (RNAseq) data, Ingenuity® Pathway Analysis (IPA ®) was used to investigate the complex role of mPT formation in inflammatory reprogramming and disease progression. LPS induced significant changes in the expression of 2715 genes, affecting 179 pathways related to mitochondrial dysfunction, defective oxidative phosphorylation, nitric oxide (NO) and reactive oxygen species (ROS) accumulation, nuclear factor, erythroid 2 like 2 (Nrf2), Toll-like receptors (TLRs), and tumor necrosis factor α receptors (TNFRs) mediated processes in wild-type mice. The disruption of CypD reduced the LPS-induced alterations in gene expression and pathways involving TNFRs and TLRs, in addition to improving survival and attenuating oxidative liver damage and the related NO- and ROS-producing pathways. CypD deficiency diminished the suppressive effect of LPS on mitochondrial function, nuclear- and mitochondrial-encoded genes, and mitochondrial DNA (mtDNA) quantity, which could be critical in improving survival. Our data propose that CypD-dependent mPT is an amplifier in inflammatory reprogramming and promotes disease progression. The mortality in human sepsis and shock is associated with mitochondrial dysfunction. Prevention of mPT by CypD disruption reduces inflammatory reprogramming, mitochondrial dysfunction, and lethality; therefore, CypD can be a novel drug target in endotoxic shock and related inflammatory diseases.
|
| |
|
| Overall design |
Comparison of CypD-/- and wild type mice in an endotoxemia model
|
| |
|
| Contributor(s) |
Veres B, Eros K, Antus C, Kalman N, Fonai F, Jakus PB, Boros E, Hegedus Z, Nagy I, Tretter L, Gallyas F Jr, Sumegi B |
| Citation(s) |
33471430 |
| Submission date |
Mar 10, 2016 |
| Last update date |
Mar 23, 2021 |
| Contact name |
Balazs Horvath |
| Organization name |
SeqOmics Biotechnology Ltd.
|
| Department |
NGSP
|
| Street address |
Vallalkozok u. 7.
|
| City |
Morahalom |
| ZIP/Postal code |
6782 |
| Country |
Hungary |
| |
|
| Platforms (1) |
| GPL15907 |
AB 5500xl Genetic Analyzer (Mus musculus) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA314843 |
| SRA |
SRP071567 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE79059_CypD_KO_LPS_vs_CypD_KO_Cl.xls.gz |
49.5 Kb |
(ftp)(http) |
XLS |
| GSE79059_CypD_KO_LPS_vs_WT_LPS_Cl.xls.gz |
35.3 Kb |
(ftp)(http) |
XLS |
| GSE79059_CypD_KO_vs_WT_Cl.xls.gz |
14.9 Kb |
(ftp)(http) |
XLS |
| GSE79059_WT_LPS_vs_WT_Cl.xls.gz |
89.8 Kb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...