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
Abstract
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.

AIM

To investigate whether lncRNA protein-disulfide isomerase-associated 3 (Pdia3) could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.

METHODS

Using normal glucose or high glucose (HG)-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress (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.

RESULTS

The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes. Next, lncRNA Pdia3 was involved in HG-induced podocyte apoptosis. Furthermore, the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.

CONCLUSION

Taken together, this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p, which might provide a potential therapeutic target for DN.

Keywords: Long noncoding RNAs, Diabetic nephropathy, Podocyte apoptosis, Endoplasmic reticulum stress, Competing endogenous RNA

Core Tip: The expression of long noncoding RNA (lncRNA) protein-disulfide isomerase-associated 3 (Pdia3) was significantly downregulated in high glucose (HG)-cultured podocytes. LncRNA Pdia3 was involved in HG-induced podocyte apoptosis. LncRNA Pdia3 overexpression attenuated HG-induced podocyte apoptosis and endoplasmic reticulum stress by acting as a competing endogenous RNA of miR-139-3p.