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Transcriptomic identification of IL-17/FOS-associated signaling in dartos fascia remodeling of pediatric concealed
Haiyang Hu1, Wenwen Liu1, Zhongsong Tu1
1Department of Pediatric Surgery, Affiliated Hospital of North Sichuan Medical College, School of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.
Insights
Pediatric concealed penis (CP) involves fibrotic dartos fascia. This study found enriched IL-17/FOS signaling pathways in CP tissues, suggesting a role in inflammation and reduced tissue compliance.
Area of Science:
- Urology
- Molecular Biology
- Pathology
Background:
- Pediatric concealed penis (CP) is a congenital anomaly linked to dartos fascia abnormalities and fibrosis.
- The molecular basis of this pathological fibrosis in CP remains poorly understood.
- Understanding the molecular drivers is crucial for potential therapeutic targets.
Purpose of the Study:
- To investigate the transcriptomic profile of dartos fascia in pediatric concealed penis.
- To identify molecular pathways involved in dartos fascia remodeling in CP.
- To explore the potential role of IL-17 signaling in CP pathogenesis.
Main Methods:
- RNA sequencing (RNA-seq) of dartos fascia from CP patients and phimosis controls.
- Bioinformatic analysis including functional enrichment.
- Validation using quantitative reverse transcription PCR (qRT-PCR), Western blot, and immunohistochemistry.
Main Results:
- RNA-seq revealed a significantly enriched IL-17-related signaling pathway in CP tissues.
- Key pathway nodes including IL-17RA, ACT1, FOS, IL-6, and PTGS2 were upregulated in CP.
- Increased FOS, IL-6, and PTGS2 correlated with fragmented elastic fibers and enhanced matrix deposition.
Conclusions:
- IL-17/FOS-associated inflammatory and remodeling signatures are present in the dartos fascia of pediatric concealed penis.
- These molecular changes may contribute to the reduced tissue compliance and fibrosis observed in CP.
- Further research is needed to establish a causal link and explore therapeutic implications.
Abstract:
Pediatric concealed penis (CP) is a congenital penile anomaly that has been associated with abnormal dartos fascia development, reduced tissue compliance, and fibrotic remodeling. While surgical correction is standard, the molecular etiology of this pathological fibrosis remains largely unexplored. This study aims to delineate the transcriptomic landscape of CP and identify candidate signaling pathways associated with dartos fascia remodeling. We performed RNA-seq on dartos fascia tissues from CP patients and phimosis control tissues, followed by bioinformatic analysis and validation using qRT-PCR, Western blot, and immunohistochemistry. RNA-seq and functional enrichment analysis identified a significantly enriched IL-17-related signaling signature in CP tissues. Experimental validation showed increased expression of key nodes such as IL-17RA, ACT1, FOS, IL-6, and PTGS2. Notably, synchronous upregulation of FOS and downstream inflammation- and remodeling-associated mediators IL-6 and PTGS2 was accompanied by fragmented elastic fibers and increased matrix deposition. These findings provide preliminary clinical tissue-based evidence that IL-17/FOS-associated inflammatory remodeling signatures are enriched in CP dartos fascia and may contribute to reduced tissue compliance and fibrosis. Further functional studies are required to determine causality.
