tRF-15:31-Arg-CCT-3-1 Improves Diabetic Kidney Disease by Reducing AATF and Alleviating Mesangial Cell Oxidative Stress and Inflammation.
- 1Department of Pediatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
- 2Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, China.
- 3Department of Pediatrics, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract
Background
Diabetic kidney disease (DKD), a primary contributor to end-stage renal disease, involves a complex interplay between oxidative stress and inflammation. Given the reported involvement of apoptosis-antagonizing transcription factor (AATF) in cellular stress and inflammatory responses, we investigated whether the anti-inflammatory effects of tRF-15:31-Arg-CCT-3-1 (tRF-15:31) are mediated through the regulation of AATF expression.Methods
The expression and biological effects of tRF-15:31 were investigated in streptozotocin (STZ)-induced DKD mice and high-glucose (HG)-treated renal mesangial cells. The involvement of AATF was examined through tRF-15:31 and AATF overexpression and siRNA-mediated knockdown of AATF.Results
Reduced expression of tRF-15:31 was observed in both STZ-induced DKD mice and HG-treated renal mesangial cells and was associated with aggravated intrarenal inflammation and oxidative stress. Overexpression of tRF-15:31 in diabetic mice significantly reduced serum creatinine levels and 24-h urinary protein excretion and alleviated renal pathological injury. Both in vivo and in vitro, tRF-15:31 overexpression markedly downregulated pro-inflammatory and oxidative stress markers, including IL-6, MCP-1, TNF-α, and malondialdehyde (MDA), while upregulating antioxidant factors such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). AATF expression was significantly elevated in STZ-induced DKD mice, whereas this upregulation was markedly suppressed by tRF-15:31 overexpression. In HG-treated mesangial cells, co-overexpression of tRF-15:31 and AATF reversed the protective effects of tRF-15:31 overexpression alone. Furthermore, siRNA-mediated knockdown of AATF significantly attenuated HG-induced inflammation and oxidative stress.Conclusion
Collectively, these findings suggest that tRF-15:31 attenuates inflammation and oxidative stress in the STZ-induced DKD model, at least in part through regulation of AATF expression. These findings provide additional mechanistic evidence for tRF-mediated regulation in DKD and support further investigation of the biological significance of the tRF-15:31-AATF regulatory relationship.
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BibTeX
@article{ning2026trf1531argcct31,
title = {{tRF-15:31-Arg-CCT-3-1 Improves Diabetic Kidney Disease by Reducing AATF and Alleviating Mesangial Cell Oxidative Stress and Inflammation.}},
author = {Beibei Ning and Chan Huang and Xuewei Liu and Yunyang Qiao and Jialing Ji and Huimin Shi and Gaoting Qu and Yajie Zhao and Weihua Gan and Aiqing Zhang},
journal = {Immunity, inflammation and disease},
year = {2026},
month = oct,
doi = {10.1002/iid3.70561},
url = {https://europepmc.org/article/MED/42895210},
note = {CC BY},
}
RIS
TY - JOUR
TI - tRF-15:31-Arg-CCT-3-1 Improves Diabetic Kidney Disease by Reducing AATF and Alleviating Mesangial Cell Oxidative Stress and Inflammation.
AU - Beibei Ning
AU - Chan Huang
AU - Xuewei Liu
AU - Yunyang Qiao
AU - Jialing Ji
AU - Huimin Shi
AU - Gaoting Qu
AU - Yajie Zhao
AU - Weihua Gan
AU - Aiqing Zhang
PY - 2026
DA - 2026/10/01
JO - Immunity, inflammation and disease
DO - 10.1002/iid3.70561
UR - https://europepmc.org/article/MED/42895210
AB - Background Diabetic kidney disease (DKD), a primary contributor to end-stage renal disease, involves a complex interplay between oxidative stress and inflammation. Given the reported involvement of apoptosis-antagonizing transcription factor (AATF) in cellular stress and inflammatory responses, we investigated whether the anti-inflammatory effects of tRF-15:31-Arg-CCT-3-1 (tRF-15:31) are mediated through the regulation of AATF expression.Methods The expression and biological effects of tRF-15:31 were investigated in streptozotocin (STZ)-induced DKD mice and high-glucose (HG)-treated renal mesangial cells. The involvement of AATF was examined through tRF-15:31 and AATF overexpression and siRNA-mediated knockdown of AATF.Results Reduced expression of tRF-15:31 was observed in both STZ-induced DKD mice and HG-treated renal mesangial cells and was associated with aggravated intrarenal inflammation and oxidative stress. Overexpression of tRF-15:31 in diabetic mice significantly reduced serum creatinine levels and 24-h urinary protein excretion and alleviated renal pathological injury. Both in vivo and in vitro, tRF-15:31 overexpression markedly downregulated pro-inflammatory and oxidative stress markers, including IL-6, MCP-1, TNF-α, and malondialdehyde (MDA), while upregulating antioxidant factors such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). AATF expression was significantly elevated in STZ-induced DKD mice, whereas this upregulation was markedly suppressed by tRF-15:31 overexpression. In HG-treated mesangial cells, co-overexpression of tRF-15:31 and AATF reversed the protective effects of tRF-15:31 overexpression alone. Furthermore, siRNA-mediated knockdown of AATF significantly attenuated HG-induced inflammation and oxidative stress.Conclusion Collectively, these findings suggest that tRF-15:31 attenuates inflammation and oxidative stress in the STZ-induced DKD model, at least in part through regulation of AATF expression. These findings provide additional mechanistic evidence for tRF-mediated regulation in DKD and support further investigation of the biological significance of the tRF-15:31-AATF regulatory relationship.
SN - 2050-4527
ER -