| First Author | Fan Y | Year | 2023 |
| Journal | Theranostics | Volume | 13 |
| Issue | 15 | Pages | 5348-5364 |
| PubMed ID | 37908721 | Mgi Jnum | J:342182 |
| Mgi Id | MGI:7546555 | Doi | 10.7150/thno.87416 |
| Citation | Fan Y, et al. (2023) Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase. Theranostics 13(15):5348-5364 |
| abstractText | Rationale: Increased methylation of key genes has been observed in kidney diseases, suggesting that the ten-eleven translocation (Tet) methyl-cytosine dioxygenase family as well as 5mC oxidation may play important roles. As a member of the Tet family, the role of Tet1 in acute kidney injury (AKI) remains unclear. Methods: Tet1 knockout mice, with or without tempol treatment, a scavenger of reactive oxygen species (ROS), were challenged with ischemia and reperfusion (I/R) injury or unilateral ureteral obstruction (UUO) injury. RNA-sequencing, Western blotting, qRT-PCR, bisulfite sequencing, chromatin immunoprecipitation, immunohistochemical staining, and dot blot assays were performed. Results: Tet1 expression was rapidly upregulated following I/R or UUO injury. Moreover, Tet1 knockout mice showed increased renal injury and renal cell death, increased ROS accumulation, G2/M cell cycle arrest, inflammation, and fibrosis. Severe renal damage in injured Tet1 knockout mice was alleviated by tempol treatment. Mechanistically, Tet1 reduced the 5mC levels in an enzymatic activity-dependent manner on the promoters of Sod1 and Sod2 to promote their expression, thus lowering injury-induced excessive ROS and reducing I/R or UUO injury. Conclusions: Tet1 plays an important role in the development of AKI by promoting SOD expression through a DNA demethylase-dependent mechanism. |
