ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis

This study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-...

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Main Authors: Yibo Wen, Junwei Wu, Qingsong Pu, Xiangfei He, Junkui Wang, Jinjin Feng, Yanping Zhang, Feng Si, Jian Guo Wen, Jinghua Yang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2023.2194440
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author Yibo Wen
Junwei Wu
Qingsong Pu
Xiangfei He
Junkui Wang
Jinjin Feng
Yanping Zhang
Feng Si
Jian Guo Wen
Jinghua Yang
author_facet Yibo Wen
Junwei Wu
Qingsong Pu
Xiangfei He
Junkui Wang
Jinjin Feng
Yanping Zhang
Feng Si
Jian Guo Wen
Jinghua Yang
author_sort Yibo Wen
collection DOAJ
description This study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-263 (25 mg/kg, oral gavage), and NBF + ABT-263 (50 mg/kg, oral gavage) groups. After cystometry, bladder and kidney tissue samples were collected for hematoxylin and eosin (HE), Masson, and Sirius red staining, and Western Blotting (WB) and qPCR detection. Primary rat bladder fibroblasts were isolated, extracted, and cultured. After co-stimulation with TGF-β1 (10 ng/mL) and ABT-263 (concentrations of 0, 0.1, 1, 10, and 100 µmol/L) for 24 h, cells were collected. Cell apoptosis was detected using CCK8, WB, immunofluorescence, and annexin/PI assays. Compared with the sham group, there was no significant difference in any physical parameters in the sham + ABT-263 (50 mg/kg) group. Compared with the NBF group, most of the markers involved in fibrosis were improved in the NBF + ABT-263 (25 mg/kg) and NBF + ABT-263 (50 mg/kg) groups, while the NBF + ABT-263 (50 mg/kg) group showed a significant improvement. When the concentration of ABT-263 was increased to 10 µmol/L, the apoptosis rate of primary bladder fibroblasts increased, and the expression of the anti-apoptotic protein BCL-xL began to decrease.ABT-263 plays an important role in relieving NBF and protecting against UUTD, which may be due to the promotion of myofibroblast apoptosis through the mitochondrial apoptosis pathway.
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publishDate 2023-12-01
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series Renal Failure
spelling doaj-art-e04796b2a622443b9d86b69f750247552025-08-20T02:16:11ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2023.2194440ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosisYibo Wen0Junwei Wu1Qingsong Pu2Xiangfei He3Junkui Wang4Jinjin Feng5Yanping Zhang6Feng Si7Jian Guo Wen8Jinghua Yang9Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaDepartment of Urology, The First People’s Hospital of Longquanyi District, Chengdu, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaDepartment of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, P.R. ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaClinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. ChinaThis study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-263 (25 mg/kg, oral gavage), and NBF + ABT-263 (50 mg/kg, oral gavage) groups. After cystometry, bladder and kidney tissue samples were collected for hematoxylin and eosin (HE), Masson, and Sirius red staining, and Western Blotting (WB) and qPCR detection. Primary rat bladder fibroblasts were isolated, extracted, and cultured. After co-stimulation with TGF-β1 (10 ng/mL) and ABT-263 (concentrations of 0, 0.1, 1, 10, and 100 µmol/L) for 24 h, cells were collected. Cell apoptosis was detected using CCK8, WB, immunofluorescence, and annexin/PI assays. Compared with the sham group, there was no significant difference in any physical parameters in the sham + ABT-263 (50 mg/kg) group. Compared with the NBF group, most of the markers involved in fibrosis were improved in the NBF + ABT-263 (25 mg/kg) and NBF + ABT-263 (50 mg/kg) groups, while the NBF + ABT-263 (50 mg/kg) group showed a significant improvement. When the concentration of ABT-263 was increased to 10 µmol/L, the apoptosis rate of primary bladder fibroblasts increased, and the expression of the anti-apoptotic protein BCL-xL began to decrease.ABT-263 plays an important role in relieving NBF and protecting against UUTD, which may be due to the promotion of myofibroblast apoptosis through the mitochondrial apoptosis pathway.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2194440ABT-263neurogenic bladderfibrosisapoptosiskidney
spellingShingle Yibo Wen
Junwei Wu
Qingsong Pu
Xiangfei He
Junkui Wang
Jinjin Feng
Yanping Zhang
Feng Si
Jian Guo Wen
Jinghua Yang
ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
Renal Failure
ABT-263
neurogenic bladder
fibrosis
apoptosis
kidney
title ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
title_full ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
title_fullStr ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
title_full_unstemmed ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
title_short ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
title_sort abt 263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis
topic ABT-263
neurogenic bladder
fibrosis
apoptosis
kidney
url https://www.tandfonline.com/doi/10.1080/0886022X.2023.2194440
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