|
| Status |
Public on Nov 22, 2017 |
| Title |
Integrated target discovery screens identify IL11 as novel therapeutic target for fibrosis [human] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cardiac fibrosis is the final common pathology in heart disease. Here we establish an integrated imaging-genomic discovery platform using primary human heart fibroblasts to identify new drug targets for cardiac fibrosis. Genome wide analyses identify IL11, a secreted cytokine amenable to therapeutic inhibition, as the leading pro-fibrotic candidate. We demonstrate an autocrine loop of IL11 activity that is critical for fibrosis and acts as a nexus of signalling convergence for multiple pro-fibrotic stimuli. IL11 signals in cis and trans via the ERK cascade to activate a programme of fibrosis primarily at the level of protein translation. Injection of IL11 to mice causes fibrosis of the heart, kidney, lung, skin and liver whereas genetic ablation of the IL11 receptor prevented fibrosis across tissues. These data define a new non-canonical fibrogenic pathway and prioritise IL11 as a novel therapeutic target for fibrosis of the heart and other organs
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| |
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| Overall design |
24 human cardiac fibroblasts. 10 basal, 10 IL11 induced, 4 TGFB1 induced. Cardiac fibroblasts were cultured in serum-free media for at least 16 hours prior to treatment with either TGFB1 or IL11.
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| Contributor(s) |
Cook SA, Schafer S, Chow K, Chothani SP, Moreno-Moral A, Widjaja AA, Pua CJ |
| Citation(s) |
29160304 |
| |
| Submission date |
Mar 23, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Sonia Chothani |
| E-mail(s) |
[email protected]
|
| Organization name |
Duke-NUS school of medicine
|
| Lab |
Prof. Stuart Cook
|
| Street address |
8 College Road
|
| City |
Singapore |
| ZIP/Postal code |
169857 |
| Country |
Singapore |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE97117 |
Integrated target discovery screens identify IL11 as novel therapeutic target for fibrosis |
|
| Relations |
| BioProject |
PRJNA380254 |
| SRA |
SRP102374 |
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