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| Status |
Public on Jan 24, 2022 |
| Title |
Deep sequencing reveals an acute inflammatory signature in chronic Peyronie’s disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Peyronie’s disease (PD) is an acquired fibrotic process affecting the tunica albuginea (TA) of the penis. The development of fibrotic plaques can lead to penile curvature/deformities, shortening and erectile dysfunction. Medical treatments are lacking due to limited understanding of disease pathophysiology. Elucidation of molecular pathways and cell types involved could lead to the development of novel disease models and conservative therapeutics.
Objective: To characterise the transcriptomic signature of plaques from PD patients and compare it to normal TA using RNA sequencing (RNAseq) and network analysis. Design, setting and participants: We collected surgical TA samples from 6 PD patients and 6 control patients where RNAseq was performed, followed by functional analysis. Our findings were validated through RT-qPCR and immunohistochemistry in other patient samples (biological validation) and tested in an in vitro PD model derived from patient samples.
Results and limitations: These findings are the first report of using human samples for transcriptome-wide analysis of genital tract fibrosis. Differential gene expression identified 1294 differentially expressed genes in PD patients. Functional analysis reveals an active inflammatory component in the chronic PD plaque. Moreover, nearly half of all overexpressed genes were regulated by NF-kB and STAT. Further analysis shows that NF-kB is TNFα and TLR-activated and JAK/STAT-signalling occurs through interleukins (IL2/IL6) /interferons (Type I/II)). This data suggests an important macrophage-related response. We validated genes from enriched pathways using RT-qPCR both in the RNAseq samples and 5 additional samples. Immunohistochemical staining for macrophages (CD68) corroborated these findings. Stimulation of PD-derived fibroblasts and myofibroblasts with TNFα revealed expression of macrophage chemoattractant protein-1 (CCL2/MCP-1).
Conclusions: Our analysis suggests that, even in an established, chronic PD-plaque, acute inflammatory pathways are still active. We show for the first time that TNFα and TLR-activation could be an important pathway in PD-pathophysiology. Additionally, we suggest that this process is potentially maintained through macrophages. Release of TNFα induce chemoattraction of more macrophages by CCL2 production of (myo)fibroblasts. Both could lead to development of novel druggable targets and more representative disease models.
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| Overall design |
6 PD samples and 6 control samples.
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| Contributor(s) |
Milenkovic U, Janky R, Hatzichristodoulou G, van Renterghem K, Gevaert T, Cellek S, Bivalacqua TJ, De Ridder D, Albersen M |
| Citation(s) |
33962884 |
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| Submission date |
Feb 01, 2019 |
| Last update date |
Jan 25, 2022 |
| Contact name |
Rekin's Janky |
| E-mail(s) |
Nucleomics.Bioinformatics@vib.be
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| Organization name |
VIB
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| Department |
Nucleomics Core
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| Street address |
Herestraat 49 Box 816
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| City |
Leuven |
| ZIP/Postal code |
B-3000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA518887 |
| SRA |
SRP183164 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126005_EdgeRTable.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE126005_RawCountsTable.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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