The potential role of differentially expressed tRNA-derived fragments in high glucose-induced podocytes

Abstract

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.

Keywords:

• diabetic kidney disease
• podocyte
• tRNA-derived fragments
• tRF-1:24-Glu-CTC-1-M2
• Gene Ontology
• Kyoto Encyclopedia of Genes and Genomes

Author contributions

W.G. and A.Z. conceptualized the study and confirmed the authenticity of the original data. Z.Z. performed experiments and wrote the manuscript. Y.Q. assisted in the preparation of the figures and tables and participated in the data analysis. J.J. helped with editing the manuscript and graphical abstract. C.H. and H.S. performed sequencing. All the authors have read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The study data are available from the corresponding authors upon reasonable request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [No. 81970664], the Natural Science Foundation of Jiangsu Province [No. BK20211385], and the Pediatric Special Fund of Jiangsu Medical Association [Nos. SYH-32034-0073 and SYH-32034-0085].