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Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy
Disruption of lysosomal homeostasis contributes to the tubulopathy of diabetic nephropathy; however, its underlying mechanisms remain unclear. Herein, we report that decreased activity of transcription factor EB (TFEB) is responsible for the disturbed lysosome biogenesis and clearance in this pathol...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786470/ https://www.ncbi.nlm.nih.gov/pubmed/35082964 http://dx.doi.org/10.1155/2022/2812493 |
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author | Wang, Shujun Jing, Kaipeng Wu, Hongluan Li, Xiaoyu Yang, Chen Li, Tingting Tang, Haoxuan Zou, Ting She, Yao Liu, Hua-feng |
author_facet | Wang, Shujun Jing, Kaipeng Wu, Hongluan Li, Xiaoyu Yang, Chen Li, Tingting Tang, Haoxuan Zou, Ting She, Yao Liu, Hua-feng |
author_sort | Wang, Shujun |
collection | PubMed |
description | Disruption of lysosomal homeostasis contributes to the tubulopathy of diabetic nephropathy; however, its underlying mechanisms remain unclear. Herein, we report that decreased activity of transcription factor EB (TFEB) is responsible for the disturbed lysosome biogenesis and clearance in this pathological process. This was confirmed by the findings that insufficient lysosomal replenishment and damaged lysosomal clearance coincided with TFEB inactivation, which was mediated by mTOR hyperactivation in the renal tubular epithelial cells (TECs) of diabetic nephropathy. Furthermore, either TFEB overexpression or pharmacological activation of TFEB enhanced lysosomal clearance via promoting lysosomal biogenesis and protected TECs by reducing apoptosis in vitro. In addition, pharmacological activation of TFEB attenuated renal tubule injury, apoptosis, and inflammation in db/db mice. In conclusion, diabetes-induced mTOR activation represses TFEB function, thereby perturbing lysosomal homeostasis through impairing lysosomal biogenesis and clearance in TECs. Moreover, TFEB activation protects TECs from diabetic injuries via restoring lysosomal homeostasis. |
format | Online Article Text |
id | pubmed-8786470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-87864702022-01-25 Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy Wang, Shujun Jing, Kaipeng Wu, Hongluan Li, Xiaoyu Yang, Chen Li, Tingting Tang, Haoxuan Zou, Ting She, Yao Liu, Hua-feng Oxid Med Cell Longev Research Article Disruption of lysosomal homeostasis contributes to the tubulopathy of diabetic nephropathy; however, its underlying mechanisms remain unclear. Herein, we report that decreased activity of transcription factor EB (TFEB) is responsible for the disturbed lysosome biogenesis and clearance in this pathological process. This was confirmed by the findings that insufficient lysosomal replenishment and damaged lysosomal clearance coincided with TFEB inactivation, which was mediated by mTOR hyperactivation in the renal tubular epithelial cells (TECs) of diabetic nephropathy. Furthermore, either TFEB overexpression or pharmacological activation of TFEB enhanced lysosomal clearance via promoting lysosomal biogenesis and protected TECs by reducing apoptosis in vitro. In addition, pharmacological activation of TFEB attenuated renal tubule injury, apoptosis, and inflammation in db/db mice. In conclusion, diabetes-induced mTOR activation represses TFEB function, thereby perturbing lysosomal homeostasis through impairing lysosomal biogenesis and clearance in TECs. Moreover, TFEB activation protects TECs from diabetic injuries via restoring lysosomal homeostasis. Hindawi 2022-01-12 /pmc/articles/PMC8786470/ /pubmed/35082964 http://dx.doi.org/10.1155/2022/2812493 Text en Copyright © 2022 Shujun Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Shujun Jing, Kaipeng Wu, Hongluan Li, Xiaoyu Yang, Chen Li, Tingting Tang, Haoxuan Zou, Ting She, Yao Liu, Hua-feng Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy |
title | Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy |
title_full | Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy |
title_fullStr | Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy |
title_full_unstemmed | Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy |
title_short | Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy |
title_sort | activation of transcription factor eb alleviates tubular epithelial cell injury via restoring lysosomal homeostasis in diabetic nephropathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786470/ https://www.ncbi.nlm.nih.gov/pubmed/35082964 http://dx.doi.org/10.1155/2022/2812493 |
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