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| Status |
Public on Nov 05, 2023 |
| Title |
Disease-specific transcriptomic changes induced by NFκB inhibition in idiopathic pulmonary fibrosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and poor prognosis. In IPF, aberrant extracellular matrix production by activated, hyperproliferative fibroblasts drives disease progression but the exact mechanisms by which this occurs remains undefined. We previously showed that inhibition of transcription factor nuclear factor kappa-B (NFκB) with ACT001 reduced pro-fibrotic fibroblast behaviors such as fibroblast-to-myofibroblast transition. The aim of this follow-up study was to characterize the transcriptional profile of primary fibroblasts treated with ACT001 and identify differences between cells from patients with IPF and non-diseased control donors. Primary lung fibroblasts derived from eight patients with IPF and eight age-matched non-diseased controls (NDC) were treated with 0, 3 or 10 µM ACT001 in the presence/absence of pro-fibrotic cytokine transforming growth factor (TGF)-β1 for 24 hours after which whole genome RNA sequencing was performed. Gene set enrichment analysis (GSEA) of the Hallmark gene sets was also completed. Although the majority of genes differentially expressed after ACT001 treatment were the same in NDC and IPF cells, several genes were uniquely changed in IPF. GSEA indicated that ACT001 treatment most upregulates the reactive oxygen species pathway. ACT001 is a water-soluble compound with a stable half-life in plasma, thus making it an attractive candidate for further investigation as a therapeutic in IPF. This study adds to the growing body of literature that demonstrates anti-fibrotic activity of NF-ĸB inhibition in the context of IPF.
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| Overall design |
Primary cultered human fibroblasts from 16 individuals, 8 with idiopathic pulmonary fibrosis (IPF) and 8 age-matched controls
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| Contributor(s) |
Jaffar J, Glaspole I, Symons K, Westall G, Wong NC |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Nov 09, 2021 |
| Last update date |
Nov 05, 2023 |
| Contact name |
Nicholas C Wong |
| E-mail(s) |
nick.wong@monash.edu
|
| Organization name |
Monash University
|
| Department |
Monash Bioinformatics Platform, Central Clinical School
|
| Street address |
Wellington Road
|
| City |
Clayton |
| State/province |
Victoria |
| ZIP/Postal code |
3800 |
| Country |
Australia |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA779019 |
| SRA |
SRP345248 |
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