Research Paper|Volume 13, Issue 6|pp 8467—8480

Determining the influence of high glucose on exosomal lncRNAs, mRNAs, circRNAs and miRNAs derived from human renal tubular epithelial cells

Sijie Zhou^1,^2,^3,^4,⁵, Jiuyuan Fang⁶, Mingyang Hu^1,^2,^3,^4,⁵, Shaokang Pan^1,^2,^3,^4,⁵, Dongwei Liu^1,^2,^3,^4,⁵, Guolan Xing^1,^2,³, Zhangsuo Liu^1,^2,^3,^4,⁵

¹Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China
²Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, P. R. China
³Research Center for Kidney Disease, Henan Province, Zhengzhou 450052, P. R. China
⁴Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China
⁵Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou 450052, P. R. China
⁶Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China

* Equal contribution

Received: August 10, 2020Accepted: January 13, 2021Published: March 10, 2021

https://doi.org/10.18632/aging.202656

Copyright: © 2021 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Diabetic nephropathy is a lethal disease that can lead to chronic kidney disease and end-stage kidney disease. Exosomes, which are nanosized extracellular vesicles, are closely involved in intercellular communication. Most importantly, exosomes play critical roles in disease occurrence and development. However, the function of exosomes in diabetic nephropathy progression has not been fully elucidated. In the present study, we determined the expression profiles and differences of lncRNAs, mRNAs, circRNAs and miRNAs in exosomes derived from human renal tubular epithelial cells with or without high glucose (HG) treatment. A total of 169 lncRNAs, 885 mRNAs, 3 circRNAs and 152 miRNAs were differentially expressed in exosomes secreted by HG-challenged HK-2 cells (HG group) compared with controls (NC group). The functions of differentially expressed mRNAs, mRNAs colocalized or coexpressed with differentially expressed lncRNAs (DElncRNAs), potential target genes of miRNAs and source genes of circRNAs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

According to these differentially expressed RNAs, we established an integrated circRNA-lncRNA-miRNA-mRNA regulatory network. In conclusion, our study suggested that exosomal lncRNAs, mRNAs, circRNAs and miRNAs participate in the progression of diabetic nephropathy and may be possible biomarkers and therapeutic targets in diabetic nephropathy.