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Integrated target discovery screens identify IL11 as novel therapeutic target for fibrosis [168 human cardiac fibroblasts]

GSE97358 Homo sapiens Expression profiling by high throughput sequencing 168 samples Submitted 2017/11/22 Platform GPL16791
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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Direct links to NCBI, no account and no request form: the whole study as GSE97358_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 168 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA381490 and SRA study SRP102952. Searching any of these in the dataset finder brings you back here.

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