Hypoxia-Induced HIF-1α Expression Promotes Neurogenic Bladder Fibrosis via EMT and Pyroptosis
Qi Li,
Yifan Hong,
Jing Chen,
Xiazhu Zhou,
Xiaomao Tian,
Yihang Yu,
Lianju Shen,
Chunlan Long,
Miao Cai,
Shengde Wu,
Guanghui Wei
Affiliations
Qi Li
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Yifan Hong
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Jing Chen
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Xiazhu Zhou
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Xiaomao Tian
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Yihang Yu
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Lianju Shen
Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China
Chunlan Long
Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China
Miao Cai
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Shengde Wu
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Guanghui Wei
Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
Background: Neurogenic bladder (NB) patients exhibit varying degrees of bladder fibrosis, and the thickening and hardening of the bladder wall induced by fibrosis will further affect bladder function and cause renal failure. Our study aimed to investigate the mechanism of bladder fibrosis caused by a spinal cord injury (SCI). Methods: NB rat models were created by cutting the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves. RNA-seq, Western blotting, immunofluorescence, cell viability and ELISA were performed to assess the inflammation and fibrosis levels. Results: The rats showed bladder dysfunction, upper urinary tract damage and bladder fibrosis after SCI. RNA-seq results indicated that hypoxia, EMT and pyroptosis might be involved in bladder fibrosis induced by SCI. Subsequent Western blot, ELISA and cell viability assays and immunofluorescence of bladder tissue confirmed the RNA-seq findings. Hypoxic exposure increased the expression of HIF-1α and induced EMT and pyroptosis in bladder epithelial cells. Furthermore, HIF-1α knockdown rescued hypoxia-induced pyroptosis, EMT and fibrosis. Conclusion: EMT and pyroptosis were involved in the development of SCI-induced bladder fibrosis via the HIF-1α pathway. Inhibition of the HIF-1α pathway may serve as a potential target to alleviate bladder fibrosis caused by SCI.