Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2024; 15(3): 519-529
Published online Mar 15, 2024. doi: 10.4239/wjd.v15.i3.519
Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina
Jian Tan, Ang Xiao, Lin Yang, Yu-Lin Tao, Yi Shao, Qiong Zhou
Jian Tan, Ang Xiao, Lin Yang, Yu-Lin Tao, Yi Shao, Qiong Zhou, Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
Co-first authors: Jian Tan and Ang Xiao.
Author contributions: Tan J, Xiao A, Yang L, Tao YL, Shao Y and Zhou Q designed the research study; Tan J, Xiao A and Yang L performed the research; Tan J and Shao Y contributed new reagents and analytic tools; Tan J and Zhou Q analyzed the data and wrote the manuscript; all authors have read and approve the final manuscript. Tan J and Xiao A contributed equally to this work as co-first authors. The reasons for designating Tan J and Xiao A as co-first authors are threefold. First, Tan J and Xiao A made equal contributions to the project research. Secondly, both Tan J and Xiao A actively participated in subsequent revisions and communication related to the paper. Finally, co-authorship serves to better exemplify collaboration within the team. In summary, we believe that designating Tan J and Xiao A as co-first authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Supported by National Natural Science Foundation of China, No. 82260211; Key Research and Development Project in Jiangxi Province, No. 20203BBG73058; Chinese Medicine Science and Technology Project in Jiangxi Province, No. 2020A0166.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Nanchang University.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zqndyfy@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: Qiong Zhou, Doctor, Professor, Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, China. zqndyfy@163.com
Received: October 12, 2023
Peer-review started: October 12, 2023
First decision: December 6, 2023
Revised: December 8, 2023
Accepted: January 18, 2024
Article in press: January 18, 2024
Published online: March 15, 2024
Abstract
BACKGROUND

Diabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, leading to visual impairment. Retinal pigment epithelium (RPE) injury is a key component of the outer blood retinal barrier, and its damage is an important indicator of DR. Receptor for activated C kinase 1 (RACK1) activates protein kinase C-ε (PKC-ε) to promote the generation of reactive oxygen species (ROS) in RPE cells, leading to apoptosis. Therefore, we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS, thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.

AIM

To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.

METHODS

In this study, Sprague-Dawley rats and adult RPE cell line-19 (ARPE-19) cells were used as in vivo and in vitro models, respectively, to explore the role of RACK1 in mediating PKC-ε in early DR. Furthermore, the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.

RESULTS

Streptozotocin-induced diabetic rats showed increased apoptosis and up-regulated expression of RACK1 and PKC-ε proteins in RPE cells following a prolonged modeling. Similarly, ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε, accompanied by an increases in ROS production, apoptosis rate, and monolayer permeability. However, silencing RACK1 significantly downregulated the expression of PKC-ε and ROS, reduced cell apoptosis and permeability, and protected barrier function.

CONCLUSION

RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.

Keywords: Diabetic retinopathy, Receptor for activated C kinase 1, Protein kinase C-ε, Adult retinal pigment epithelium cell line-19

Core Tip: To investigate the role and associated underlying mechanisms of receptor for activated C kinase 1 (RACK1) in the development of early diabetic retinopathy (DR). In this study, Sprague-Dawley rats and adult retinal pigment epithelium (RPE) cell line-19 cells were used as in vivo and in vitro models, respectively, to explore the role of RACK1 in mediating protein kinase C-ε in early DR. RACK1 plays a significant role in the development of early DR, and may serve as a potential therapeutic target for DR by regulating the apoptosis and barrier function of RPE cells.