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| Status |
Public on Apr 19, 2012 |
| Title |
A specific Peroxisome Proliferator-Activated Receptor (PPAR)-delta agonist is hepatoprotective and attenuates liver fibrogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
PPARδ is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle and liver. The aim of our study was to assess the effect of either the well-validated PPARδ agonist GW501516, or a novel PPARδ agonist KD3010 in mouse models of liver fibrosis. KD3010, but not GW501516, treated mice had markedly less liver injury induced by carbon tetrachloride (CCl4) injections. Deposition of extracellular matrix proteins was lower in the KD3010 group as compared to the vehicle or GW501516 treated group. Interestingly, profibrogenic CTGF was significantly induced by GW501516, but not KD3010, following CCl4 treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for three weeks. Hepatocytes were identified as targets for PPARδ agonist, and primary hepatocytes treated with KD3010 showed decreased serum starvation or CCl4-induced cell death, while GW501516 treated hepatocytes were not protected. KD3010 treatment of hepatocytes decreased reactive oxygen species (ROS) production after CCl4 exposure. In conclusion, our data demonstrate that a novel PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis. Given the oral availability and the favorable pharmacologic profile of KD3010, ligand activation of PPARδ represents an attractive and promising target for patients with chronic liver diseases.
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| Overall design |
Total RNA was extracted from primary mouse hepatocytes treated with DMSO or PPARd agonists (KD3010, GW1516)
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| Contributor(s) |
Yu RT, Iwaisako K, Schnabl B, Yu E, Evans RM |
| Citation(s) |
22538808 |
| Submission date |
Sep 14, 2011 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Ruth T Yu |
| Organization name |
Salk Institute
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| Department |
Gene Expression Lab
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| Lab |
Ronald Evans
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| Street address |
10010 N Torrey Pines Rd
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (6)
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| GSM796341 |
mouse primary hepatocytes, DMSO, technical replicate 1 |
| GSM796342 |
mouse primary hepatocytes, DMSO, technical replicate 2 |
| GSM796343 |
mouse primary hepatocytes, KD3010, technical replicate 1 |
| GSM796344 |
mouse primary hepatocytes, KD3010, technical replicate 2 |
| GSM796345 |
mouse primary hepatocytes, GW1516, technical replicate 1 |
| GSM796346 |
mouse primary hepatocytes, GW1516, technical replicate 2 |
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| Relations |
| BioProject |
PRJNA147447 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE32121_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE32121_non-normalized.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| GSE32121_normalized.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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