TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease
Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease...
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| Format: | Article |
| Language: | English |
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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.2024.2338933 |
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| author | Yunxia Du Ming Wu Shan Song Yawei Bian Yonghong Shi |
| author_facet | Yunxia Du Ming Wu Shan Song Yawei Bian Yonghong Shi |
| author_sort | Yunxia Du |
| collection | DOAJ |
| description | Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood. In this study, we found that TXNIP knockout suppressed renal fibrosis and activation of mammalian target of rapamycin complex 1 (mTORC1) and restored transcription factor EB (TFEB) and autophagy activation in diabetic kidneys. Simultaneously, TXNIP interference inhibited epithelial-to-mesenchymal transformation (EMT), collagen I and fibronectin expression, and mTORC1 activation, increased TFEB nuclear translocation, and promoted autophagy restoration in HK-2 cells exposed to high glucose (HG). Rapamycin, an inhibitor of mTORC1, increased TFEB nuclear translocation and autophagy in HK-2 cells under HG conditions. Moreover, the TFEB activators, curcumin analog C1 and trehalose, effectively restored HG-induced autophagy, and abrogated HG-induced EMT and collagen I and fibronectin expression in HK-2 cells. Taken together, these findings suggest that TXNIP deficiency ameliorates renal fibrosis by regulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseases. |
| format | Article |
| id | doaj-art-0af5b511cc5c4bf28748a90dcafc76af |
| 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-0af5b511cc5c4bf28748a90dcafc76af2025-01-23T04:17:49ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2338933TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseaseYunxia Du0Ming Wu1Shan Song2Yawei Bian3Yonghong Shi4Department of Pathology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, Hebei Medical University, Shijiazhuang, ChinaThioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood. In this study, we found that TXNIP knockout suppressed renal fibrosis and activation of mammalian target of rapamycin complex 1 (mTORC1) and restored transcription factor EB (TFEB) and autophagy activation in diabetic kidneys. Simultaneously, TXNIP interference inhibited epithelial-to-mesenchymal transformation (EMT), collagen I and fibronectin expression, and mTORC1 activation, increased TFEB nuclear translocation, and promoted autophagy restoration in HK-2 cells exposed to high glucose (HG). Rapamycin, an inhibitor of mTORC1, increased TFEB nuclear translocation and autophagy in HK-2 cells under HG conditions. Moreover, the TFEB activators, curcumin analog C1 and trehalose, effectively restored HG-induced autophagy, and abrogated HG-induced EMT and collagen I and fibronectin expression in HK-2 cells. Taken together, these findings suggest that TXNIP deficiency ameliorates renal fibrosis by regulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseases.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2338933Autophagydiabetic kidney diseasemTORC1TXNIPTFEB |
| spellingShingle | Yunxia Du Ming Wu Shan Song Yawei Bian Yonghong Shi TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease Renal Failure Autophagy diabetic kidney disease mTORC1 TXNIP TFEB |
| title | TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease |
| title_full | TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease |
| title_fullStr | TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease |
| title_full_unstemmed | TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease |
| title_short | TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease |
| title_sort | txnip deficiency attenuates renal fibrosis by modulating mtorc1 tfeb mediated autophagy in diabetic kidney disease |
| topic | Autophagy diabetic kidney disease mTORC1 TXNIP TFEB |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2338933 |
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