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| Status |
Public on Feb 05, 2024 |
| Title |
WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Renal fibrosis is a common pathological endpoint that is challenging to reverse in chronic kidney disease (CKD) independently of the underlying causes. Although myofibroblasts are mainly responsible for the accumulation of a fibrillar collagen-rich extracellular matrix (ECM), recent reports revealed their heterogeneity in proliferative and fibrotic activities, mirroring specific metabolic states that drive fibrosis. Here, we investigate the role of E3 ubiquitin-protein ligase WWP2 in the metabolic reprogramming of renal myofibroblasts in fibrosis. The tubulointerstitial expression of WWP2 contributes to the progression of fibrosis in CKD patients and in pre-clinical models of CKD. WWP2 deficiency leads to increased fatty acid oxidation, boosting mitochondrial respiration, promoting myofibroblast proliferation and arresting pro-fibrotic activation, thus ameliorating kidney fibrosis. Specifically, WWP2 suppresses the transcription of PGC-1α, which mediates the metabolic and proliferative changes in fibrotic myofibroblasts. Pharmacological intervention targeting PGC-1α reverses the pro-fibrotic effect of WWP2. These findings reveal a previously unappreciated WWP2-PGC-1α axis underlying the metabolic reprogramming of myofibroblasts during renal fibrosis, which could provide a new target for therapeutic intervention in CKD.
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| Overall design |
RNA-seq analysis of fibroblast derived from wildtype and WWP2-/- mouse kidney with and without TGFβ1 treatment.
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| Contributor(s) |
Chen H, Chow G, Guo J, Petretto EG |
| Citation(s) |
38502123 |
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| Submission date |
Aug 23, 2023 |
| Last update date |
May 07, 2024 |
| Contact name |
Jing Guo |
| E-mail(s) |
jing.guo@duke-nus.edu.sg
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| Organization name |
Duke-NUS Medical School
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| Department |
Center for Computational Biology
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| Street address |
8 Collage Road, DUKE-NUS Medical School, level 5
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| City |
Singapore |
| State/province |
State... |
| ZIP/Postal code |
169857 |
| Country |
Singapore |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (20)
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| GSM7729945 |
myofibroblast, KO, untreated, rep4 |
| GSM7729946 |
myofibroblast, KO, untreated, rep5 |
| GSM7729947 |
myofibroblast, KO, treated, rep1 |
| GSM7729948 |
myofibroblast, KO, treated, rep2 |
| GSM7729949 |
myofibroblast, KO, treated, rep3 |
| GSM7729950 |
myofibroblast, KO, treated, rep4 |
| GSM7729951 |
myofibroblast, KO, treated, rep5 |
| GSM7729952 |
myofibroblast, WT, untreated, rep1 |
| GSM7729953 |
myofibroblast, WT, untreated, rep2 |
| GSM7729954 |
myofibroblast, WT, untreated, rep3 |
| GSM7729955 |
myofibroblast, WT, untreated, rep4 |
| GSM7729956 |
myofibroblast, WT, untreated, rep5 |
| GSM7729957 |
myofibroblast, WT, treated, rep1 |
| GSM7729958 |
myofibroblast, WT, treated, rep2 |
| GSM7729959 |
myofibroblast, WT, treated, rep3 |
| GSM7729960 |
myofibroblast, WT, treated, rep4 |
| GSM7729961 |
myofibroblast, WT, treated, rep5 |
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| This SubSeries is part of SuperSeries: |
| GSE241504 |
WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS |
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| Relations |
| BioProject |
PRJNA1008461 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241503_combined.count.matrix.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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