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| Status |
Public on Aug 01, 2018 |
| Title |
Alteration in the transcriptome of lung resident fibroblast upon genetic knockdown of Wilms' tumor1 transcription factor |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of stromal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and stromal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Recent published reports from our lab demonstrated the aberrant activation of Wilms' tumor1 (WT1) transcription factor in lung resident fibroblast and myofibroblast in IPF lung biopsies and the mouse model of transforming growth factor-α (TGFα) and bleomycin induced fibrosis. In this study, we sought to determine the role of WT1 in transcriptome changes in lung resident fibroblast during pulmonary fibrosis. Our results showed that WT1 regulates the transcriptional changes that are required for the fibroblast activation processes such fibroproliferation, myofibroblast transformation and extracellular matrix deposition during pulmonary fibrosis. Finally, this study demonstrates that WT1 is a critical regulator of fibroblast activation in IPF and hence serve as a target for therapeutic intervention.
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| |
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| Overall design |
mRNA profiles of cultured fibrotic lung resident fibroblast isolated from TGFα mice and treated with Control or WT1-specific siRNA.
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| |
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| Contributor(s) |
Sontake V, Chen J, Medvedovic M, Madala SK |
| Citation(s) |
30135315 |
| |
| Submission date |
Feb 05, 2018 |
| Last update date |
Jun 11, 2019 |
| Contact name |
Mario Medvedovic |
| Organization name |
University of Cincinnati
|
| Department |
Department of Environmental Health
|
| Lab |
Laboratory for Statistical Genomics and Systems Biology
|
| Street address |
3223 Eden Av. ML 56
|
| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45267-0056 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
|
| Samples (6)
|
| GSM2981765 |
Resident fibroblast transfected with stealth control siRNA, VS1 |
| GSM2981766 |
Resident fibroblast transfected with stealth control siRNA, VS2 |
| GSM2981767 |
Resident fibroblast transfected with stealth control siRNA, VS3 |
| GSM2981768 |
Resident fibroblast transfected with stealth WT1 siRNA, V4 |
| GSM2981769 |
Resident fibroblast transfected with stealth WT1 siRNA, V5 |
| GSM2981770 |
Resident fibroblast transfected with stealth WT1 siRNA, V6 |
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| Relations |
| BioProject |
PRJNA433015 |
| SRA |
SRP132232 |
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