Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2024; 15(1): 92-104
Published online Jan 15, 2024. doi: 10.4239/wjd.v15.i1.92
Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease
Lu-Lu Han, Sheng-Hai Wang, Ming-Yan Yao, Hong Zhou
Lu-Lu Han, Hong Zhou, Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Lu-Lu Han, Ming-Yan Yao, Department of Endocrinology, Baoding No. 1 Central Hospital, Baoding 071000, Hebei Province, China
Sheng-Hai Wang, Department of Critical Care Medicine, The Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
Co-first authors: Lu-Lu Han and Sheng-Hai Wang.
Author contributions: Zhou H contributed to the conceptualization, methodology, resources, writing-reviewing and editing of this manuscript; Han LL participated in the visualization, writing-original draft preparation of this study; Wang SH took part in the investigation and data curation of this article; Yao MY was major in the interpretation of data, manuscript revision, language and format editing; and all authors were responsible for the content and proposed critical comments on the manuscript, as well as approving final version submission.
Supported by the Nature Science Foundation of Hebei Province, No. H2023104011.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, all research protocols were approved by Ethical Committee of the Second Hospital of Hebei Medical University (approval number: 2022-R059, 28 February 2022) and the Chinese Clinical Trial Registry (approval number: ChiCTR2200066055). A written informed consent was demanded from each participant before they joined this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Zhou, PhD, Chief Physician, Doctor, Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China. zhoubs2013@163.com
Received: September 7, 2023
Peer-review started: September 7, 2023
First decision: November 17, 2023
Revised: November 27, 2023
Accepted: December 25, 2023
Article in press: December 25, 2023
Published online: January 15, 2024
Abstract
BACKGROUND

Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney.

AIM

To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis.

METHODS

Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.

RESULTS

Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis.

CONCLUSION

Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.

Keywords: Urinary exosome, MicroRNA-145-5p, MicroRNA-27a-3p, Diabetic kidney disease, Diagnostic biomarkers

Core Tip: Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus (DM). Novel biomarkers and effective therapeutic targets for DKD are needed in clinical settings. In this study, urinary exosomal microRNA-145-5p (miR-145-5p) and miR-27a-3p from patients with DKD were associated with kidney injury progression in type 2 DM patients. MiR-145-5p was highly specific and sensitive to DKD. It may be involved in the signaling pathways related to the pathological processes of DKD. Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers and therapy targets for DKD.