Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2023; 14(8): 1234-1248
Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1234
Potential role of microRNA-503 in Icariin-mediated prevention of high glucose-induced endoplasmic reticulum stress
Bao-Lin Su, Liang-Liang Wang, Liang-You Zhang, Shu Zhang, Qiang Li, Gang-Yi Chen
Bao-Lin Su, Liang-Liang Wang, Liang-You Zhang, Shu Zhang, Qiang Li, Gang-Yi Chen, Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong Province, China
Author contributions: Su BL and Chen GY designed the study and interpreted the data; Wang LL and Zhang LY performed all experiments and drafted the manuscript; Zhang S and Li Q collected and analyzed the data; Su BL and Chen GY reviewed the manuscript.
Supported by The First Affiliated Hospital of Guangzhou University of Chinese Medicine Innovation and Strengthening Fund, No. 2019QN14.
Institutional review board statement: The study does not involve human experiments.
Institutional animal care and use committee statement: The study was reviewed and approved by the Animal Care and Use Committee of Guangzhou University of TCM, No. GZTCMF1-2022053. All postoperative animal care and surgical interventions complied with the NIH Guide for Care and Use of Laboratory Animals. All surgery and euthanasia were performed under sodium pentobarbital anesthesia (200 mg/kg) by intraperitoneal injection. Every effort was made to minimize suffering.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The datasets used or/and analyzed during the current study are available from the corresponding author on reasonable request.
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: Gang-Yi Chen, MD, Doctor, Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, No. 16 Jichang Road, Guangzhou 510405, Guangdong Province, China. gangyichen5001@126.com
Received: April 20, 2023
Peer-review started: April 20, 2023
First decision: June 1, 2023
Revised: June 12, 2023
Accepted: July 7, 2023
Article in press: July 7, 2023
Published online: August 15, 2023
ARTICLE HIGHLIGHTS
Research background

The study focuses on the effects of high glucose (HG) levels in diabetes and its implications on kidney function. It builds upon existing literature indicating that protein misfolding and endoplasmic reticulum (ER) stress are prevalent in kidney diseases, including diabetic nephropathy (DN) and chronic kidney disease. In addition, the flavonol glycoside Icariin (ICA), a traditional Chinese medicine (TCM), has shown potential in attenuating ER stress, which may potentially prevent or halt the progression of kidney diseases.

Research motivation

The research aimed to explore the potential of ICA as a treatment for HG-induced cellular damage, focusing on its interaction with specific microRNAs and proteins that contribute to renal cell damage. Given the increasing interest in the use of TCM as a safer and efficient alternative therapy, understanding the cellular mechanisms of ICA could provide valuable insights for potential therapeutic interventions in DN.

Research objectives

The primary goal was to investigate the effects of ICA on HG-treated kidney cells, with a particular emphasis on the role of miR-503 and sirtuin 4 (SIRT4) in the pathogenesis of HG-induced kidney injury. The study's findings could further the understanding of the mechanisms of ICA, paving the way for future research into its effectiveness and reliability as a treatment for DN.

Research methods

The research used in vitro experiments to study the effects of ICA on HG-induced cell injury and ER stress in renal cells. The methods adopted included overexpression and inhibition of miR-503 and measuring levels of ER stress markers. The study also conducted a dual luciferase assay to determine whether SIRT4 is a direct target of miR-503.

Research results

The study identified that ICA ameliorates HG-induced cell injury by reducing the expression of miR-503. This research also discovered that miR-503 directly targets SIRT4, a novel finding in the field. However, some problems remain, such as establishing the causative role of miR-503 in DN and validating the results in other cell types associated with diabetes.

Research conclusions

This study proposes a new theory suggesting the role of the ICA/miR-503/SIRT4 axis in the pathogenesis of HG-induced renal cell injury. Additionally, it presents a new method of using ICA treatment to regulate the miR-503/SIRT4 axis, thereby protecting cells from HG-induced cell damage and ER stress.

Research perspectives

Future research should focus on validating these findings in animal models and different diabetic-associated cell types like podocytes or β-cells. Further studies should also explore the therapeutic efficacy of Icariin or miR-503 in clinical settings for conditions like DN, ultimately advancing our understanding of the ICA/miR-503/SIRT4 axis's role in managing diabetes.