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| Status |
Public on Nov 17, 2022 |
| Title |
Therapeutically enabled mammalian kidney repair and regeneration |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The kidney has large regenerative capacity that is impeded when injured renal tubular epithelial cells (TECs) undergo SNAI1-driven partial epithelial mesenchymal transition (pEMT). Here we investigate the role of IL11 in TEC pEMT and kidney repair. Wild-type mice with acute kidney injury (AKI) upregulate IL11 in TECs triggering an ERK/P90RSK/GSK3β axis of SNAI1 expression leading to impaired renal function, which is abrogated in Il11 null mice. In mouse models of AKI, a neutralizing IL11 antibody promotes kidney regeneration, while attenuating pEMT, fibrosis and kidney dysfunction. In TECs, TGFβ1 induces autocrine IL11/ERK-dependent pEMT leading to paracrine, IL11-mediated fibroblast activation. Mice with TEC-specific deletion of Il11ra1 are protected from pEMT, inflammation, fibrosis and renal failure. In a mouse model of chronic kidney disease, administration of anti-IL11 reverses fibrosis, regenerates kidney parenchyma and restores renal function. Therapeutic inhibition of IL11 signaling appears permissive for promoting kidney regeneration and improving kidney function.
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| Overall design |
24 samples
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| Contributor(s) |
Widjaja A, Cook S |
| Citation(s) |
36470928 |
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| Submission date |
Mar 21, 2022 |
| Last update date |
Jan 04, 2023 |
| Contact name |
Sonia Chothani |
| E-mail(s) |
e0081753@u.duke.nus.edu
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| Organization name |
Duke-NUS school of medicine
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| Lab |
Prof. Stuart Cook
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| Street address |
8 College Road
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| City |
Singapore |
| ZIP/Postal code |
169857 |
| Country |
Singapore |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (16)
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| GSM5963810 |
Tubular epithelial cells_stimulated_1 hour_rep1 |
| GSM5963811 |
Tubular epithelial cells_stimulated_1 hour_rep2 |
| GSM5963812 |
Tubular epithelial cells_stimulated_1 hour_rep3 |
| GSM5963813 |
Tubular epithelial cells_stimulated_1 hour_rep4 |
| GSM5963814 |
Tubular epithelial cells_stimulated_24 hour_rep1 |
| GSM5963815 |
Tubular epithelial cells_stimulated_24 hour_rep2 |
| GSM5963816 |
Tubular epithelial cells_stimulated_24 hour_rep3 |
| GSM5963817 |
Tubular epithelial cells_stimulated_24 hour_rep4 |
| GSM5963818 |
Tubular epithelial cells_stimulated_6 hour_rep1 |
| GSM5963819 |
Tubular epithelial cells_stimulated_6 hour_rep2 |
| GSM5963820 |
Tubular epithelial cells_stimulated_6 hour_rep3 |
| GSM5963821 |
Tubular epithelial cells_stimulated_6 hour_rep4 |
| GSM5963822 |
Tubular epithelial cells_baseline_rep1 |
| GSM5963823 |
Tubular epithelial cells_baseline_rep2 |
| GSM5963824 |
Tubular epithelial cells_baseline_rep3 |
| GSM5963825 |
Tubular epithelial cells_baseline_rep4 |
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| Relations |
| BioProject |
PRJNA818306 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199080_RNAseq_full_all.counts.txt.gz |
5.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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