Yin Ni, Xie Xian, Li Dan, Yang Shikun, Liu Yan, Tang Yongzhong, Zhang Hao, Zhang Wei
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China.
iScience. 2025 Feb 5;28(3):111954. doi: 10.1016/j.isci.2025.111954. eCollection 2025 Mar 21.
tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs are involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in IRI-AKI mice and its overexpression mitigated renal dysfunction, morphological damage, and apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assay and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3'-UTR of mRNA. Furthermore, the protective efficacy of tRF-Val was notably weakened by -overexpressing plasmids. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.
转运RNA衍生片段（tRFs）在细胞过程中发挥关键作用，我们之前曾报道tRFs参与缺血再灌注损伤诱导的急性肾损伤（IRI-AKI）。然而，tRFs在IRI-AKI中的具体作用仍不清楚。本研究旨在阐明tRF-Val-TAC-004（tRF-Val）对IRI-AKI的影响并揭示其潜在机制。我们的观察结果显示，IRI-AKI小鼠中tRF-Val显著下调，其过表达减轻了IRI-AKI小鼠的肾功能障碍、形态损伤和细胞凋亡，而其抑制则加剧了这些影响。在用tRF-Val模拟物或抑制剂转染后，CoCl处理的BUMPT细胞中也出现了类似结果。机制上，双荧光素酶报告基因检测和AGO-RIP qPCR分析表明，tRF-Val通过靶向mRNA的3'-UTR抑制Apaf1表达。此外，Apaf1过表达质粒显著削弱了tRF-Val的保护作用。总之，这些新发现揭示了tRF-Val通过抑制Apaf1介导的细胞凋亡对IRI-AKI的保护作用。
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