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Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • الموضوع:
      NF-kappa B*/metabolism ; Urinary Bladder, Neurogenic*/pathology; Rats ; Animals ; Transforming Growth Factor beta1/metabolism ; Urinary Bladder/pathology ; Pyroptosis ; Rats, Sprague-Dawley ; Signal Transduction ; Fibrosis ; Epithelial Cells/metabolism
    • نبذة مختصرة :
      Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-β1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-β1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-β1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-β1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders.
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    • Grant Information:
      NCRCCHD-2020-GP-04 Guanghui Wei
    • Contributed Indexing:
      Keywords: NF-κB signaling pathway; fibrosis; neurogenic bladder; pyroptosis; spinal cord injury
    • الرقم المعرف:
      0 (NF-kappa B)
      0 (Transforming Growth Factor beta1)
    • الموضوع:
      Date Created: 20230714 Date Completed: 20230717 Latest Revision: 20230718
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC10342524
    • الرقم المعرف:
      10.3390/ijms241311160
    • الرقم المعرف:
      37446339