TRNA-Derived Fragments in Podocytes with Adriamycin-Induced Injury Reveal the Potential Mechanism of Idiopathic Nephrotic Syndrome.

Shanwen Li,Weihua Gan,Xiaowei He,Yiwen Liu,Huimin Shi,Aiqing Zhang,Xiagang Luo,Jun Wang,Gaoting Qu,Xianli Wen

doi:10.1155/2020/7826763

Abstract

Idiopathic nephrotic syndrome (INS) is a disease involving injury to podocytes in the glomerular filtration barrier, and its specific causes have not been elucidated. Transfer RNA-derived fragments (tRFs), products of precise tRNA cleavage, have been indicated to play critical roles in various diseases. Currently, there is no relevant research on the role of tRFs in INS. This study intends to explore the changes in and importance of tRFs during podocyte injury in vitro and to further analyze the potential mechanism of INS. Differentially expressed tRFs in the adriamycin-treated group were identified by high-throughput sequencing and further verified by quantitative RT-PCR. In total, 203 tRFs with significant differential expression were identified, namely, 102 upregulated tRFs and 101 downregulated tRFs (q < 0.05, ∣log2FC | ≥2). In particular, AS-tDR-008924, AS-tDR-011690, tDR-003634, AS-tDR-013354, tDR-011031, AS-tDR-001008, and AS-tDR-007319 were predicted to be involved in podocyte injury by targeting the Gpr, Wnt, Rac1, and other genes. Furthermore, gene ontology analysis showed that these differential tRFs were strongly associated with podocyte injury processes such as protein binding, cell adhesion, synapses, the actin cytoskeleton, and insulin-activate receptor activity. KEGG pathway analysis predicted that they participated in the PI3K-Akt signaling pathway, Wnt signaling pathway, and Ras signaling pathway. It was reported that these pathways contribute to podocyte injury. In conclusion, our study revealed that changes in the expression levels of tRFs might be involved in INS. Seven of the differentially expressed tRFs might play important roles in the process of podocyte injury and are worthy of further study.

Highlights

Idiopathic nephrotic syndrome (INS) is a glomerular disease that predominantly occurs in children and is characterized by massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema [1, 2]
To investigate podocyte injuryrelated tRNA-derived fragments, the differentiated podocytes were treated with adriamycin for 24 hours to establish the podocyte injury model
The results showed that nephrin and podocin were upregulated in differentiated podocytes compared with undifferentiated podocytes, proving successful differentiation of podocytes (Figure 1(b))

Summary

Introduction

Idiopathic nephrotic syndrome (INS) is a glomerular disease that predominantly occurs in children and is characterized by massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema [1, 2]. The viewpoint that podocyte injury is the basic pathology of INS has become well established. It is of great importance to explore the mechanism of podocyte injury in idiopathic nephrotic syndrome. Our previous research showed that tRFs may regulate the differentiation of podocytes and the process of chronic kidney disease [9]. A recent study showed that plasma exosomal tRFs might be diagnostic biomarkers for osteoporosis [10]. There have been no relevant reports on the relationship between tRFs and INS in a podocyte injury model

Methods

Results

Discussion

Conclusion