Role of tRNA derived fragments in renal ischemia–reperfusion injury

Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). tRNA derived fragments (tRFs/tiRNAs) are groups of small noncoding RNAs derived from tRNAs. To date, the role of tRFs/tiRNAs in renal IRI has not been reported. Herein, we aimed to investigate the involvement of tRFs/tiRNAs in the occurrence and development of ischemia–reperfusion-induced AKI. Moderate/severe renal IRI mouse models were established by bilateral renal pedicle clamping. The tRF/tiRNA profiles of healthy controls and moderate/severe IRI-stressed kidney tissues were sequenced by Illumina NextSeq 500. Candidate differentially expressed tiRNAs were further verified by RT-qPCR. Biological analysis was also performed. Overall, 152 tRFs/tiRNAs were differentially expressed in the moderate ischemic injury group compared with the normal control group (FC > 2, p 2, p Our results indicated that tRFs/tiRNAs were involved in renal IRI. These tRFs/tiRNAs may be effective partly via regulation of renal immunity, inflammation and metabolism processes. Candidate genes, including tiRNA-Gly-GCC-003, tiRNA-Lys-CTT-003, and tiRNA-His-GTG-002, might be potential biomarkers and therapeutic targets of ischemia–reperfusion injury-induced acute kidney injury.缺血再灌注损伤（Ischemia-reperfusion injury, IRI）是急性肾损伤（acute kidney injury, AKI）的主要致病因素之一。tRNA衍生片段（tRNA derived fragments, tRFs/tiRNAs）是一类由转运RNA剪切产生的小型非编码RNA。截至目前，tRFs/tiRNAs在肾IRI中的作用尚未见文献报道。本研究旨在探讨tRFs/tiRNAs在缺血再灌注诱导的AKI发生发展中的参与机制。研究通过双侧肾蒂夹闭法构建中度/重度肾IRI小鼠模型，利用Illumina NextSeq 500测序平台对健康对照组及中度/重度IRI应激的肾组织进行tRF/tiRNA表达谱测序，并通过实时定量聚合酶链反应（Real-time quantitative polymerase chain reaction, RT-qPCR）对候选差异表达tiRNAs进行验证，同时开展生物学功能分析。结果显示，与正常对照组相比，中度缺血损伤组中共鉴定出152个差异表达的tRFs/tiRNAs（FC>2，P<0.05）。本研究结果表明，tRFs/tiRNAs参与了肾IRI的病理进程，其可能通过调控肾脏免疫、炎症及代谢过程发挥部分作用。候选tiRNA包括tiRNA-Gly-GCC-003、tiRNA-Lys-CTT-003及tiRNA-His-GTG-002，有望成为缺血再灌注损伤诱导的急性肾损伤的潜在生物标志物及治疗靶点。