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| Status |
Public on May 06, 2022 |
| Title |
IL-11 is a therapeutic target in idiopathic pulmonary fibrosis |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where invasive pulmonary myofibroblasts secrete collagen and destroy lung integrity. Here we show that IL-11 is upregulated in the lung of IPF patients, associated with disease severity and is secreted from IPF fibroblasts. In vitro, IL-11 stimulates lung fibroblasts to become invasive, ACTA2+ve, collagen secreting myofibroblasts, in an ERK-dependent fashion. In mice, fibroblast-specific transgenic expression or administration of Il-11 drives lung fibroblast-to-myofibroblast transformation and causes lung fibrosis. Il11ra1 deleted mice, whose lung fibroblasts are unresponsive to pro-fibrotic stimulation, are protected from fibrosis in the bleomycin mouse model of pulmonary fibrosis. We generated an IL-11 neutralising antibody that blocks lung fibroblast activation downstream of multiple stimuli and reverses myofibroblast activation. In therapeutic studies, anti-IL-11 treatment both prevented and reversed lung fibrosis, which was accompanied by diminished Erk activation. These data prioritise IL-11 as a drug target for lung fibrosis and IPF.
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| Overall design |
For human in vitro samples, 3 commercial and 2 patient-derived normal lung fibroblasts were stimulated with either TGFB or IL11 and compared with baseline accounting for the sample effect (matched design) and the source effect. Mouse in vitro samples were also treated similarly and were analyzed using a matched design. Mouse in vivo samples have 4 replicates per treatment group.
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| Contributor(s) |
Ng B, Dong J, D’Agostino G, Viswanathan S, Widjaja AA, Lim W, Ko NJ, Tan J, Chothani SP, Huang B, Xie C, Pua CJ, Chacko A, Guimarães-Camboa N, Evans SM, Byrne AJ, Maher TM, Liang J, Jiang D, Noble PW, Schafer S, Cook SA |
| Citation(s) |
31554736 |
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| Submission date |
May 09, 2019 |
| Last update date |
Mar 16, 2023 |
| Contact name |
Eleonora Adami |
| E-mail(s) |
[email protected]
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| Organization name |
Duke-NUS Medical School
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| Department |
CVMD
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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 (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (39)
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| Relations |
| BioProject |
PRJNA542170 |
| SRA |
SRP197373 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130983_Counts_Human_Stim.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE130983_Counts_Lung_AB_Mouse.txt.gz |
769.7 Kb |
(ftp)(http) |
TXT |
| GSE130983_Counts_Mouse_Fib_KO_and_Stim.txt.gz |
830.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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