糖尿病肾病(DKD)的患病率逐年增加。足细胞的损害和损失发生在DKD的早期。tRNA衍生片段(tRFs),源自tRNA前体或成熟tRNA,与各种疾病有关。在这项研究中,确定了tRF,并探讨了它们在高糖(HG)治疗引起的足细胞损伤中的作用。对用HG处理的足细胞进行高通量测序以鉴定差异表达的tRF。进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)分析。nephrin的表达水平,波多辛,在过表达tRF-1:24-Glu-CTC-1-M2(tRF-1:24)并伴随HG治疗后,在足细胞中测量结蛋白。总共确定了647个tRF,在HG组中鉴定出89个差异表达的tRF(|log2FC|≥0.585;p≤0.05),其中53个tRF下调,36个tRF上调。通过实时定量聚合酶链反应(RT-qPCR)检测差异表达最高的10个tRFs,这些结果与测序结果一致。GO分析显示,生物过程,细胞成分,tRF最富集的分子功能术语是细胞过程,细胞解剖实体,和绑定。KEGG通路分析显示,tRFs可能参与了与生长激素相关的信号通路,磷脂酶D,干细胞多能性的调节,和T-/B-细胞受体。tRF-1:24的过表达,tRF-1是表达差异最大的tRF之一,减轻HG诱导的足细胞损伤。因此,tRF可能是DKD足细胞损伤的潜在生物标志物。
The prevalence of diabetic kidney disease (DKD) is increasing annually. Damage to and loss of podocytes occur early in DKD. tRNA-derived fragments (tRFs), originating from tRNA precursors or mature tRNAs, are associated with various illnesses. In this study, tRFs were identified, and their roles in podocyte injury induced by high-glucose (HG) treatment were explored. High-throughput sequencing of podocytes treated with HG was performed to identify differentially expressed tRFs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression levels of nephrin, podocin, and desmin were measured in podocytes after overexpression of tRF-1:24-Glu-CTC-1-M2 (tRF-1:24) and concomitant HG treatment. A total of 647 tRFs were identified, and 89 differentially expressed tRFs (|log2FC| ≥ 0.585; p ≤ .05) were identified in the HG group, of which 53 tRFs were downregulated and 36 tRFs were upregulated. The 10 tRFs with the highest differential expression were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and these results were consistent with the sequencing results. GO analysis revealed that the biological process, cellular component, and molecular function terms in which the tRFs were the most enriched were cellular processes, cellular anatomical entities, and binding. KEGG pathway analysis revealed that tRFs may be involved in signaling pathways related to growth hormones, phospholipase D, the regulation of stem cell pluripotency, and T-/B-cell receptors. Overexpression of tRF-1:24, one of the most differentially expressed tRFs, attenuated podocyte injury induced by HG. Thus, tRFs might be potential biomarkers for podocyte injury in DKD.