Expression profiles of tRNA‑derived fragments in high glucose‑treated tubular epithelial cells

Abstract

Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNA produced by the cleavage of pre-and mature tRNAs, are involved in various diseases. Renal tubulointerstitial fibrosis is a common final pathway in diabetic nephropathy (DN) in which hyperglycemia-induced tubular extracellular matrix (ECM) accumulation serves a vital role. The present study aimed to detect and investigate the role of tRFs in the accumulation of tubular ECM. Differentially expressed tRFs were analysed with high-throughput sequencing in primary mouse tubular epithelial cells treated with high glucose (HG). The Gene Ontology (GO) was used to analyze the potential molecular functions of these differentially expressed tRFs, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the associated signaling pathways involved in these differentially expressed tRFs. tRF-1:30-Gln-CTG-4 was overexpressed using tRF-1:30-Gln-CTG-4 mimic, followed by HG treatment. A total of 554 distinct tRFs were detected and 64 differentially expressed tRFs (fold change >2; P<0.05) were identified in tubular epithelial cells following high glucose (HG) treatment, among which 27 were upregulated and 37 were downregulated. Ten selected tRFs with the greatest difference (fold change >2; P<0.05) were verified to be consistent with small RNA-sequencing data, of which tRF-1:30-Gln-CTG-4 showed the most pronounced difference in expression and was significantly decreased in response to HG. GO analysis indicated that the differentially expressed tRFs were associated with 'cellular process', 'biological regulation' and 'metabolic process'. An analysis of the KEGG database suggested that these differentially expressed tRFs were involved in 'autophagy' and signaling pathways for 'forkhead box O', 'the mammalian target of rapamycin' and 'mitogen-activated protein kinase'. Finally, the overexpression of tRF-1:30-Gln-CTG-4 ameliorated HG-induced ECM accumulation in tubular epithelial cells. Therefore, the present study demonstrated that there may be a significant association between tRFs and HG-induced ECM accumulation in tubular epithelial cells; these differentially expressed tRFs warrant further study to explore the pathogenesis of DN.

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

“…Our high-throughput sequencing results also showed the involvement of various types of tRFs, with tRF-5s accounting for the highest proportion. This result was similar to the sequencing result for HG-treated renal tubular epithelial cells observed in our previous study [ 20 ]. It is hypothesized that tRF-5s play a particularly important role in DKD, and this supposition needs to be tested via further study in the future.…”

“…Previous studies by our team showed that tRFs affect podocyte differentiation and podocyte injury in patients with idiopathic nephrotic syndrome [ 18 , 19 ]. The expression profiles of renal tubular epithelial cells induced by high glucose (HG) were also explored [ 20 ]. Thus, these previous studies initially demonstrated the promising clinical applications of tRFs.…”

tRNA-Derived Small RNAs: A Novel Regulatory Small Noncoding RNA in Renal Diseases

“…Notably, a similar decrease in tRF-1:30-Gln-CTG-4 expression was also observed in the serum of patients with DN. Intriguingly, the researchers found that overexpressing tRF-1:30-Gln-CTG-4 in renal tubular epithelial cells led to a reduction in extracellular matrix deposition induced by HG, suggesting a potential protective role [ 98 ]. In a subsequent phase of their investigation, the researcher examined diabetic patients with and without albuminuria, identifying six differentially expressed tsRNAs (tRF5-GluCTC, tRF5-AlaCGC, tRF5-ValCAC, tRF5-GlyCCC, tRF3-GlyGCC, and tRF3-IleAAT) [ 99 ].…”