Identification of inflammation-related biomarkers and therapeutic targets for neurogenic bladder fibrosis via multi-omics analysis

  • Comput Biol Med. 2025 Sep;196(Pt A):110721. doi: 10.1016/j.compbiomed.2025.110721.
Qi Li  1 ,  Lei Lv  2 ,  Yanping Zhang  2 ,  Junkui Wang  3 ,  Xingchen Liu  4 ,  Zhan Wang  2 ,  Junjie Zhang  5 ,  Shengli Zhang  5 ,  Yibo Wen  2 ,  Luping Li  6 ,  Yingzhong Fan  7 ,  Jianguo Wen  8
Affiliations
  • 1. Henan Joint International Paediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 2. Henan Joint International Paediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 3. Henan Joint International Paediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 4. Henan Joint International Paediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Obstetrics and Gynecology, Xinyang Central Hospital, Xinyang, 464000, Henan, China.
  • 5. Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 6. Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: [email protected].
  • 7. Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: [email protected].
  • 8. Henan Joint International Paediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address: [email protected].
PMID: 40618693 DOI: 10.1016/j.compbiomed.2025.110721
Abstract

Inflammatory responses play a crucial role in the progression of pediatric neurogenic bladder (NB)-associated fibrosis; however, their specific contributions remain poorly understood. This study aimed to identify inflammation-related biomarkers for diagnosing NB fibrosis and to explore potential therapeutic drugs. The NB rat model was established by spinal nerve severing, followed by single-cell and bulk RNA Sequencing of bladder tissues. Through integrated analysis-including differentially expressed genes (DEGs), inflammation-related genes (IRGs), WGCNA, and machine learning-we identified four diagnostic biomarkers: HIF-1α, IL-1β, CD40, and IL10RA. Molecular Biology experiments validated the elevated expression of these biomarkers in NB patients. Single-cell RNA Sequencing further localized their overexpression to epithelial cells, interstitial cells, and T cells. Connectivity Map (cMAP) analysis identified the MEK Inhibitor PD-0325901 as a potential anti-fibrotic agent, which was subsequently confirmed through in vivo and in vitro experiments. Molecular docking simulations demonstrated that PD-0325901 exerts its therapeutic effects by targeting HIF-1α. Collectively, our findings not only provide novel diagnostic biomarkers for NB fibrosis but also propose PD-0325901 as a promising candidate for the treatment of fibrosis.

Keywords
Biomarker; Children; Fibrosis; Inflammation; Neurogenic bladder.
Products
Inhibitors & Agonists
Other Products