FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner
Background Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (SAP). Previous investigations have revealed the involvement of FTO alpha-ketoglutarate-dependent dioxygenase (FTO) and aquaporin 3 (AQP3) in AKI. Therefore, the aim of this study is to explore the associati...
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2322037 |
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| author | Xinghui Li Qi Liang Lu Liu Shujun Chen Yong Li Yu Pu |
| author_facet | Xinghui Li Qi Liang Lu Liu Shujun Chen Yong Li Yu Pu |
| author_sort | Xinghui Li |
| collection | DOAJ |
| description | Background Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (SAP). Previous investigations have revealed the involvement of FTO alpha-ketoglutarate-dependent dioxygenase (FTO) and aquaporin 3 (AQP3) in AKI. Therefore, the aim of this study is to explore the association of FTO and AQP3 on proximal tubular epithelial cell damage in SAP-induced AKI.Methods An in-vitro AKI model was established in human proximal tubular epithelial cells (PTECs) HK-2 via tumor necrosis factor-α (TNF-α) induction (20 ng/mL), after which FTO and AQP3 expression was manipulated and quantified by quantitative real-time PCR and Western blotting. The viability and apoptosis of PTECs under various conditions, and reactive oxygen species (ROS), superoxide dismutase (SOD), and malonaldehyde (MDA) levels within these cells were measured using commercial assay kits and flow cytometry. Methylated RNA immunoprecipitation and mRNA stability assays were performed to elucidate the mechanism of FTO-mediated N6-methyladenosine (m6A) modification. Western blotting was performed to quantify β-catenin protein levels in the PTECs.Results FTO overexpression attenuated the TNF-α-induced decrease in viability and SOD levels, elevated apoptosis, increased levels of ROS and MDA, and diminished TNF-α-induced AQP3 expression and reduced β-catenin expression, but its silencing led to contradictory results. FTO negatively modulates AQP3 levels in RTECs in an m6A-depednent manner and compromises AQP3 stability. In addition, all FTO overexpression-induced effects in TNF-α-induced PTECs were neutralized following AQP3 upregulation.Conclusion FTO alleviates TNF-α-induced damage to PTECs in vitro by targeting AQP3 in an m6A-dependent manner. |
| format | Article |
| id | doaj-art-164f10bde592449e824617ea3b8109d6 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-164f10bde592449e824617ea3b8109d62025-01-23T04:17:47ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2322037FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent mannerXinghui Li0Qi Liang1Lu Liu2Shujun Chen3Yong Li4Yu Pu5Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Medical Imaging Key Laboratory of Sichuan Province, Nanchong, Sichuan Province, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, ChinaDepartment of Radiology, Affiliated Hospital of North Sichuan Medical College, Medical Imaging Key Laboratory of Sichuan Province, Nanchong, Sichuan Province, ChinaDepartment of Radiology, Affiliated Hospital of North Sichuan Medical College, Medical Imaging Key Laboratory of Sichuan Province, Nanchong, Sichuan Province, ChinaDepartment of Radiology, Affiliated Hospital of North Sichuan Medical College, Medical Imaging Key Laboratory of Sichuan Province, Nanchong, Sichuan Province, ChinaDepartment of Radiology, Affiliated Hospital of North Sichuan Medical College, Medical Imaging Key Laboratory of Sichuan Province, Nanchong, Sichuan Province, ChinaBackground Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (SAP). Previous investigations have revealed the involvement of FTO alpha-ketoglutarate-dependent dioxygenase (FTO) and aquaporin 3 (AQP3) in AKI. Therefore, the aim of this study is to explore the association of FTO and AQP3 on proximal tubular epithelial cell damage in SAP-induced AKI.Methods An in-vitro AKI model was established in human proximal tubular epithelial cells (PTECs) HK-2 via tumor necrosis factor-α (TNF-α) induction (20 ng/mL), after which FTO and AQP3 expression was manipulated and quantified by quantitative real-time PCR and Western blotting. The viability and apoptosis of PTECs under various conditions, and reactive oxygen species (ROS), superoxide dismutase (SOD), and malonaldehyde (MDA) levels within these cells were measured using commercial assay kits and flow cytometry. Methylated RNA immunoprecipitation and mRNA stability assays were performed to elucidate the mechanism of FTO-mediated N6-methyladenosine (m6A) modification. Western blotting was performed to quantify β-catenin protein levels in the PTECs.Results FTO overexpression attenuated the TNF-α-induced decrease in viability and SOD levels, elevated apoptosis, increased levels of ROS and MDA, and diminished TNF-α-induced AQP3 expression and reduced β-catenin expression, but its silencing led to contradictory results. FTO negatively modulates AQP3 levels in RTECs in an m6A-depednent manner and compromises AQP3 stability. In addition, all FTO overexpression-induced effects in TNF-α-induced PTECs were neutralized following AQP3 upregulation.Conclusion FTO alleviates TNF-α-induced damage to PTECs in vitro by targeting AQP3 in an m6A-dependent manner.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2322037Acute kidney injuryfat-mass and obesity-associated proteinaquaporin 3proximal tubular epithelial cellsN6-methyladenosine modification |
| spellingShingle | Xinghui Li Qi Liang Lu Liu Shujun Chen Yong Li Yu Pu FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner Renal Failure Acute kidney injury fat-mass and obesity-associated protein aquaporin 3 proximal tubular epithelial cells N6-methyladenosine modification |
| title | FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner |
| title_full | FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner |
| title_fullStr | FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner |
| title_full_unstemmed | FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner |
| title_short | FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner |
| title_sort | fto attenuates tnf α induced damage of proximal tubular epithelial cells in acute pancreatitis induced acute kidney injury via targeting aqp3 in an n6 methyladenosine dependent manner |
| topic | Acute kidney injury fat-mass and obesity-associated protein aquaporin 3 proximal tubular epithelial cells N6-methyladenosine modification |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2322037 |
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