| First Author | Yang Y | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 1334 |
| PubMed ID | 36906617 | Mgi Jnum | J:369956 |
| Mgi Id | MGI:7445829 | Doi | 10.1038/s41467-023-37043-5 |
| Citation | Yang Y, et al. (2023) DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice. Nat Commun 14(1):1334 |
| abstractText | Kidney injury initiates epithelial dedifferentiation and myofibroblast activation during the progression of chronic kidney disease. Herein, we find that the expression of DNA-PKcs is significantly increased in the kidney tissues of both chronic kidney disease patients and male mice induced by unilateral ureteral obstruction and unilateral ischemia-reperfusion injury. In vivo, knockout of DNA-PKcs or treatment with its specific inhibitor NU7441 hampers the development of chronic kidney disease in male mice. In vitro, DNA-PKcs deficiency preserves epithelial cell phenotype and inhibits fibroblast activation induced by transforming growth factor-beta 1. Additionally, our results show that TAF7, as a possible substrate of DNA-PKcs, enhances mTORC1 activation by upregulating RAPTOR expression, which subsequently promotes metabolic reprogramming in injured epithelial cells and myofibroblasts. Taken together, DNA-PKcs can be inhibited to correct metabolic reprogramming via the TAF7/mTORC1 signaling in chronic kidney disease, and serve as a potential target for treating chronic kidney disease. |
