Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury
Background: Chronic kidney disease (CKD) has become a worldwide health problem and the incidence rate and mortality of CKD have been rising. Renal fibrosis (RF) is the final common pathological feature of almost all kinds of CKD and Epithelial-mesenchymal transition (EMT) is the predominant stage of...
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Elsevier
2025-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580824002711 |
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| author | Ping Sun Haihui Yang Binying Min Yongfu Li Jun Wang Mo Chen Diping Yu Wenjuan Sun |
| author_facet | Ping Sun Haihui Yang Binying Min Yongfu Li Jun Wang Mo Chen Diping Yu Wenjuan Sun |
| author_sort | Ping Sun |
| collection | DOAJ |
| description | Background: Chronic kidney disease (CKD) has become a worldwide health problem and the incidence rate and mortality of CKD have been rising. Renal fibrosis (RF) is the final common pathological feature of almost all kinds of CKD and Epithelial-mesenchymal transition (EMT) is the predominant stage of RF. β-catenin is a key component of the Wnt signaling pathway, which has been fully proven to promote EMT. However, the underlying mechanism of β-catenin in EMT during the pathogenesis of RF is yet to be determined. Objective: This study was designed to investigate the effects of β-catenin on RF-related EMT and further investigate its underlying mechanism. Methods: Human proximal tubular epithelial cell (HK-2) was treated with hypoxia to construct RF injury cell model. The viability of cells was determined by CCK-8 assay. Immunofluorescence was used to detect α-SMA content. Expressions of β-catenin, Brachyury and RF-related proteins were measured by Western blot. The correlation between β-catenin and Brachyury was detected by ChIP-qPCR and dual luciferase reporter assay. Results: We found β-catenin was overexpressed in hypoxia-induced HK-2 cells. In the RF cell model, silencing of β-catenin weakened the EMT and fibrogenesis activity of HK-2 cells. Mechanistically, we found β-catenin binds to T-cell factor (TCF) to activate Brachyury, which is a positive player in EMT. Further studies clarified that Brachyury was responsible for β-catenin-promoted the EMT and HK-2 cell injury under hypoxia condition. Conclusions: Herein, we demonstrated that β-catenin is overexpressed in hypoxia-induced HK-2 cells and promotes EMT and cell injury via activating Brachyury. These findings suggest that targeting β-catenin/Brachyury may be an effective new approach for treating RF. |
| format | Article |
| id | doaj-art-da977e1e67d74d5ab58cd7d6efe5f440 |
| institution | DOAJ |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-da977e1e67d74d5ab58cd7d6efe5f4402025-08-20T03:15:16ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-014110190710.1016/j.bbrep.2024.101907Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating BrachyuryPing Sun0Haihui Yang1Binying Min2Yongfu Li3Jun Wang4Mo Chen5Diping Yu6Wenjuan Sun7Ministry of Science and Education, Pu'er People's Hospital, Pu'er, Yunnan, China; Ministry of Science and Education, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, ChinaVice Dean, Pu'er People's Hospital, Pu'er, Yunnan, ChinaDepartment of Ultrasound, Pu'er People's Hospital, Pu'er, Yunnan, ChinaMinistry of Science and Education, Pu'er People's Hospital, Pu'er, Yunnan, ChinaMedical Laboratory Center, Pu'er People's Hospital, Pu'er, Yunnan, ChinaDepartment of Gastrointestinal and Burn Plastic Surgery, Pu'er People's Hospital, Pu'er, Yunnan, ChinaDepartment of Pathology, Pu'er People's Hospital, Pu'er, Yunnan, ChinaDepartment of Nephrology, Pu'er People's Hospital, Pu'er, Yunnan, China; Corresponding author.Background: Chronic kidney disease (CKD) has become a worldwide health problem and the incidence rate and mortality of CKD have been rising. Renal fibrosis (RF) is the final common pathological feature of almost all kinds of CKD and Epithelial-mesenchymal transition (EMT) is the predominant stage of RF. β-catenin is a key component of the Wnt signaling pathway, which has been fully proven to promote EMT. However, the underlying mechanism of β-catenin in EMT during the pathogenesis of RF is yet to be determined. Objective: This study was designed to investigate the effects of β-catenin on RF-related EMT and further investigate its underlying mechanism. Methods: Human proximal tubular epithelial cell (HK-2) was treated with hypoxia to construct RF injury cell model. The viability of cells was determined by CCK-8 assay. Immunofluorescence was used to detect α-SMA content. Expressions of β-catenin, Brachyury and RF-related proteins were measured by Western blot. The correlation between β-catenin and Brachyury was detected by ChIP-qPCR and dual luciferase reporter assay. Results: We found β-catenin was overexpressed in hypoxia-induced HK-2 cells. In the RF cell model, silencing of β-catenin weakened the EMT and fibrogenesis activity of HK-2 cells. Mechanistically, we found β-catenin binds to T-cell factor (TCF) to activate Brachyury, which is a positive player in EMT. Further studies clarified that Brachyury was responsible for β-catenin-promoted the EMT and HK-2 cell injury under hypoxia condition. Conclusions: Herein, we demonstrated that β-catenin is overexpressed in hypoxia-induced HK-2 cells and promotes EMT and cell injury via activating Brachyury. These findings suggest that targeting β-catenin/Brachyury may be an effective new approach for treating RF.http://www.sciencedirect.com/science/article/pii/S2405580824002711Chronic kidney diseaseRenal fibrosisEMTβ-cateninBrachyury |
| spellingShingle | Ping Sun Haihui Yang Binying Min Yongfu Li Jun Wang Mo Chen Diping Yu Wenjuan Sun Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury Biochemistry and Biophysics Reports Chronic kidney disease Renal fibrosis EMT β-catenin Brachyury |
| title | Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury |
| title_full | Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury |
| title_fullStr | Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury |
| title_full_unstemmed | Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury |
| title_short | Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury |
| title_sort | effect of β catenin on hypoxia induced epithelial mesenchymal transition in hk 2 cells by regulating brachyury |
| topic | Chronic kidney disease Renal fibrosis EMT β-catenin Brachyury |
| url | http://www.sciencedirect.com/science/article/pii/S2405580824002711 |
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