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

Jialing Ji; Ju Rong; Hui Zheng; Huimin Shi; Gaoting Qu; Shanwen Li; Weihua Gan; Aiqing Zhang

doi:10.3892/etm.2022.11725

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

Exp Ther Med. 2022 Nov 23;25(1):26. doi: 10.3892/etm.2022.11725. eCollection 2023 Jan.

Authors

Jialing Ji¹, Ju Rong¹, Hui Zheng¹, Huimin Shi¹, Gaoting Qu¹, Shanwen Li¹, Weihua Gan¹, Aiqing Zhang¹

Affiliation

¹ Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, P.R. China.

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.

Keywords: diabetic nephropathy; extracellular matrix; tRF-1:30-Gln-CTG-4; tRNA-derived fragment; tubular epithelial cells.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China (grant no. 81970664), Natural Science Foundation of Jiangsu Province (grants nos. BK20191082 and BK20211385) and 789 Outstanding Talent Program of SAHNMU (grants nos. 789ZYRC202080119 and 789ZYRC202090251).