Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2024; 15(2): 260-274
Published online Feb 15, 2024. doi: 10.4239/wjd.v15.i2.260
Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p
Yin-Xi He, Ting Wang, Wen-Xian Li, Yan-Xia Chen
Yin-Xi He, Department of Orthopaedic Trauma, The Third Hospital of Shijiazhuang, Shijiazhuang 050000, Hebei Province, China
Ting Wang, Yan-Xia Chen, Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Wen-Xian Li, Department of Endocrinology, The First Hospital of Zhangjiakou, Zhangjiakou 075000, Hebei Province, China
Author contributions: Chen YX conceived or supervised the study; He YX designed experiments; He YX and Wang T performed experiments; Li WX analyzed data; He YX and Chen YX wrote the manuscript; Chen YX made manuscript revisions; and all authors have read and approve the final manuscript.
Supported by the Natural Science Funds for Young Scholar of Hebei, China, No. H2020206108; and the Subject of Health Commission of Hebei, China, No. 20210151.
Institutional animal care and use committee statement: All experimental procedures were in accordance with the institutional animal care and use committee and approved by the Animal Care and Ethics Committee of Second Hospital of Hebei Medical University (approval No. 2022-AE051).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at chenbs2013@163.com.
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: Yan-Xia Chen, Doctor, Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang 050000, Hebei Province, China. chenyx@hebmu.edu.cn
Received: September 24, 2023
Peer-review started: September 24, 2023
First decision: December 6, 2023
Revised: December 13, 2023
Accepted: January 15, 2024
Article in press: January 15, 2024
Published online: February 15, 2024
Processing time: 132 Days and 18.3 Hours
ARTICLE HIGHLIGHTS
Research background

Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy (DN). The regulatory relationship between long noncoding RNAs (lncRNAs) and podocyte apoptosis has recently become another research hot spot in the DN field. LncRNAs are a potential therapeutic target for alleviating DN development to search for novel lncRNAs and alter the expression of specific lncRNAs.

Research motivation

We here investigated lncRNA expression profiles and the associated competing endogenous RNA (ceRNA) network using high-throughput RNA-sequencing (RNA-seq) technologies in normal glucose (5.5 mmol/L, NG group) and high glucose (25 mmol/L, HG group) cultured mouse podocytes. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the function of differentially expressed lncRNAs.

Research objectives

The present study investigated the function and underlying molecular mechanism of novel lncRNAs in endoplasmic reticulum stress (ERS)-podocyte apoptosis, providing the hope of developing a new and effective therapeutic strategy against DN.

Research methods

Using NG or HG-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA protein-disulfide isomerase-associated 3 (Pdia3) on podocyte apoptosis and ERS were explored. LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction. Relative cell viability was detected through the cell counting kit-8 colorimetric assay. The podocyte apoptosis rate in each group was measured through flow cytometry. The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay. Finally, western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.

Research results

LncRNA Pdia3 was down-expressed in HG-cultured podocytes. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS in HG-cultured podocytes. LncRNA Pdia3 regulated podocyte apoptosis by serving as a ceRNA of miR-139-3p. Inhibition of miR-139-3p attenuated podocyte apoptosis and ERS in HG-cultured podocytes.

Research conclusions

This study provided evidence that lncRNA Pdia3 downregulation is a significant contributing factor for podocyte apoptosis in DN. LncRNA Pdia3 downregulation could induce ERS and podocyte injury by serving as a ceRNA of miR-139-3p, thereby leading to DN progression.

Research perspectives

In the future, whether the findings obtained in vitro can be applied to in vivo DN needs to be investigated. We intend to detect the expression and underlying molecular mechanism of lncRNA Pdia3 in DN patients.