Novel Insights: Differentially Expressed tsRNAs Modulate the Advance of Early-Stage Diabetic Nephropathy in Mice

Background: Early tubular injury is the initiating factor of diabetic nephropathy. It is still unclear the effects of transfer RNA-derived small RNA (tsRNA) in the early tubular injury of diabetic nephropathy. This study was designed to investigate the effects and mechanisms of tsRNA in renal tubular injury caused by diabetes nephropathy.Methods: High-throughput RNA sequencing was applied to recognize differential tsRNAs of primary renal tubular epithelial cells, which were extracted from 12-week-old male db/m and db/db mice. The tsRNAs were further identified by quantitative real-time polymerase chain reaction (qRT-PCR). The target genes of tsRNAs were predicted using MiRanda. The Gene On-tology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) databases were used to explore the related physiological functions and signal pathways of target genes.Results: Seven tsRNAs with differential expression were identified, and the expression of six tsRNAs was verified to the same trend as high-throughput RNA sequencing by RT-qPCR. In comparison to db/m mice, the expression of 4 tsRNAs was up-regulated (tRF-51:72-chrM.Met-CAT, tRF-52:71-chrM.Arg-TCG, tRF-1:32-Val-CAC-4, tRF-+1:T17-Asn-GTT-3-9), and the ex -pression of 3 tsRNAs was down-regulated (tRF-1:30-Gly-GCC-2-M3, tRF-57:76-Tyr-GTA-2-M2, tRF-+1:T16-Asp-GTC-1-6) in db/db mice. Furthermore, the target genes of tsRNAs were mainly linked to the toll-like receptor signaling pathway, circadian entrainment pathway, longevity regulating pathway, and hypoxia-inducible factor 1 (HIF-1) signaling pathway.Conclusions: The tsRNAs are involved in the pathology of renal tubular injury induced by diabetic nephropathy, and may be associated with some signaling pathway, including the HIF-1 signaling pathways, the longevity regulatory pathway, the circadian regulatory pathway and the toll-like receptor signaling pathway.