Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis
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 lu...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/11160 |
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| author | Jing Chen Qi Li Yifan Hong Xiazhu Zhou Chengjun Yu Xiaomao Tian Jie Zhao Chunlan Long Lianju Shen Shengde Wu Guanghui Wei |
| author_facet | Jing Chen Qi Li Yifan Hong Xiazhu Zhou Chengjun Yu Xiaomao Tian Jie Zhao Chunlan Long Lianju Shen Shengde Wu Guanghui Wei |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | 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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| issn | 1661-6596 1422-0067 |
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| spelling | doaj.art-7f654acb6f4e4a7990f8edd7feacf7072023-11-18T16:49:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124131116010.3390/ijms241311160Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder FibrosisJing Chen0Qi Li1Yifan Hong2Xiazhu Zhou3Chengjun Yu4Xiaomao Tian5Jie Zhao6Chunlan Long7Lianju Shen8Shengde Wu9Guanghui Wei10Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, ChinaMost 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.https://www.mdpi.com/1422-0067/24/13/11160neurogenic bladderspinal cord injuryNF-κB signaling pathwaypyroptosisfibrosis |
| spellingShingle | Jing Chen Qi Li Yifan Hong Xiazhu Zhou Chengjun Yu Xiaomao Tian Jie Zhao Chunlan Long Lianju Shen Shengde Wu Guanghui Wei Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis International Journal of Molecular Sciences neurogenic bladder spinal cord injury NF-κB signaling pathway pyroptosis fibrosis |
| title | Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis |
| title_full | Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis |
| title_fullStr | Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis |
| title_full_unstemmed | Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis |
| title_short | Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis |
| title_sort | inhibition of the nf κb signaling pathway alleviates pyroptosis in bladder epithelial cells and neurogenic bladder fibrosis |
| topic | neurogenic bladder spinal cord injury NF-κB signaling pathway pyroptosis fibrosis |
| url | https://www.mdpi.com/1422-0067/24/13/11160 |
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