2. Academic Validation
  3. Identification of inflammation-related biomarkers and therapeutic targets for neurogenic bladder fibrosis via multi-omics analysis

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

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: Lee447@126.com.
  • 7 Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: fanyingzhong2@163.com.
  • 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: jgwen@zzu.edu.cn.
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.

Figures
Products
Inhibitors & Agonists