Work

tRF‐15:31‐Arg‐CCT‐3‐1 Improves Diabetic Kidney Disease by Reducing AATF and Alleviating Mesangial Cell Oxidative Stress and Inflammation

Year: 2026

Type: article

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.

Source: Immunity Inflammation and Disease

DOI: 10.1002/iid3.70561