Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2025; 16(2): 101538
Published online Feb 15, 2025. doi: 10.4239/wjd.v16.i2.101538
Transcriptome and single-cell profiling of the mechanism of diabetic kidney disease
Ying Zhou, Xiao Fang, Lin-Jing Huang, Pei-Wen Wu
Ying Zhou, Lin-Jing Huang, Pei-Wen Wu, Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Xiao Fang, Department of Kidney Transplantation, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China
Lin-Jing Huang, Pei-Wen Wu, Department of Endocrinology National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou 350212, Fujian Province, China
Lin-Jing Huang, Pei-Wen Wu, Clinical Research Center for Metabolic Diseases of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Lin-Jing Huang, Pei-Wen Wu, Fujian Key Laboratory of Glycolipid and Bone Mineral Metabolism, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Lin-Jing Huang, Pei-Wen Wu, Diabetes Research Institute of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Co-first authors: Ying Zhou and Xiao Fang.
Author contributions: Zhou Y and Fang X contributed equally to this study as co-first authors. Wu PW conceived and designed research, edited and revised manuscript, and approved final version of manuscript; Zhou Y performed experiments; Fang X analyzed data and interpreted results of experiments; Huang LJ and Zhou Y prepared figures and drafted manuscript.
Supported by Joint Funds for the Innovation of Science and Technology, Fujian Province, No. 2021Y9106; Fujian Provincial Health Technology Project, No. 2021GGA033; and the Natural Science Foundation of Fujian Province, No. 2024J011234.
Institutional animal care and use committee statement: All experimental protocols involving animals were conducted in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Fujian Animal Research Ethics Commission (license No. IACUC FJMU 2022-0587).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The raw data (GSE30529, GSE142025, and GSE131882) were acquired from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/).
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Pei-Wen Wu, PhD, Chief Physician, Professor, Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Fuzhou 350005, Fujian Province, China. wpeiwen@fjmu.edu.cn
Received: September 22, 2024
Revised: October 29, 2024
Accepted: November 26, 2024
Published online: February 15, 2025
Processing time: 100 Days and 14.1 Hours
Abstract
BACKGROUND

The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome may play an important role in diabetic kidney disease (DKD). However, the exact link remains unclear.

AIM

To investigate the role of the NLRP3 inflammasome in DKD.

METHODS

Using datasets from the Gene Expression Omnibus database, 30 NLRP3 inflammasome-related genes were identified. Differentially expressed genes were selected using differential expression analysis, whereas intersecting genes were selected based on overlapping differentially expressed genes and NLRP3 inflammasome-related genes. Subsequently, three machine learning algorithms were used to screen genes, and biomarkers were identified by overlapping the genes from the three algorithms. Potential biomarkers were validated by western blotting in a db/db mouse model of diabetes.

RESULTS

Two biomarkers, sirtuin 2 (SIRT2) and caspase 1 (CASP1), involved in the Leishmania infection pathway were identified. Both biomarkers were expressed in endothelial cells. Pseudo-temporal analysis based on endothelial cells showed that DKD mostly occurs during the mid-differentiation stage. Western blotting results showed that CASP1 expression was higher in the DKD group than in the control group (P < 0.05), and SIRT2 content decreased (P < 0.05).

CONCLUSION

SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.

Keywords: Diabetic kidney disease; Single-cell RNA sequencing analysis; NOD-like receptor thermal protein domain associated protein 3; Sirtuin 2; Caspase 1

Core Tip: The NOD-like receptor thermal protein domain associated protein 3 inflammasome is implicated in diabetic kidney disease. Our study makes a significant contribution to the literature by identifying sirtuin 2 and caspase 1 as potential biomarkers for diabetic kidney disease, providing new insights into the molecular mechanisms involving the NOD-like receptor thermal protein domain associated protein 3 inflammasome, and suggesting potential targets for diagnosis and treatment, which are crucial for clinical and policy implications.