Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2022; 13(4): 338-357
Published online Apr 15, 2022. doi: 10.4239/wjd.v13.i4.338
Roles of transient receptor potential channel 6 in glucose-induced cardiomyocyte injury
Shi-Jun Jiang
Shi-Jun Jiang, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Jiang SJ conceived and designed the study, collected, analyzed, and interpreted the data, wrote the manuscript, provided critical revisions that are important for the intellectual content, and approved the final version of the manuscript.
Institutional review board statement: This study was conducted with approval from the Ethics Committee of Hubei Provincial Center for Disease Control and Prevention (No. 202110009).
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals.
Conflict-of-interest statement: There are no relevant financial or non-financial interests to disclose.
Data sharing statement: No additional data are available.
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: Shi-Jun Jiang, MM, Research Fellow, School of Basic Medicine, Huazhong University of Science and Technology, No. 13 Aviation Road, Qiaokou District, Wuhan 430030, Hubei Province, China. jiangsj_89756@163.com
Received: October 2, 2021
Peer-review started: October 2, 2021
First decision: January 12, 2022
Revised: January 18, 2022
Accepted: March 15, 2022
Article in press: March 15, 2022
Published online: April 15, 2022
Abstract
BACKGROUND

Diabetic cardiomyopathy (DCM) is a serious complication of end-stage diabetes that presents symptoms such as cardiac hypertrophy and heart failure. The transient receptor potential channel 6 (TRPC6) protein is a very important selective calcium channel that is closely related to the development of various cardiomyopathies.

AIM

To explore whether TRPC6 affects cardiomyocyte apoptosis and proliferation inhibition in DCM.

METHODS

We compared cardiac function and myocardial pathological changes in wild-type mice and mice injected with streptozotocin (STZ), in addition to comparing the expression of TRPC6 and P-calmodulin-dependent protein kinase II (P-CaMKII) in them. At the same time, we treated H9C2 cardiomyocytes with high glucose and then evaluated the effects of addition of SAR, a TRPC6 inhibitor, and KN-93, a CaMKII inhibitor, to such H9C2 cells in a high-glucose environment.

RESULTS

We found that STZ-treated mice had DCM, decreased cardiac function, necrotic cardiomyocytes, and limited proliferation. Western blot and immunofluorescence were used to detect the expression levels of various appropriate proteins in the myocardial tissue of mice and H9C2 cells. Compared to those in the control group, the expression levels of the apoptosis-related proteins cleaved caspase 3 and Bax were significantly higher in the experimental group, while the expression of the proliferation-related proteins proliferating cell nuclear antigen (PCNA) and CyclinD1 was significantly lower. In vivo and in vitro, the expression of TRPC6 and P-CaMKII increased in a high-glucose environment. However, addition of inhibitors to H9C2 cells in a high-glucose environment resulted in alleviation of both apoptosis and proliferation inhibition.

CONCLUSION

The inhibition of apoptosis and proliferation of cardiomyocytes in a high-glucose environment may be closely related to activation of the TRPC6/P-CaMKII pathway.

Keywords: Diabetic cardiomyopathy, Apoptosis, Proliferation, H9C2 cells, Transient receptor potential channel 6, P-calmodulin dependent protein kinase II

Core Tip: Diabetic cardiomyopathy is a serious complication of end-stage diabetes that presents symptoms such as cardiac hypertrophy and heart failure. The transient receptor potential channel 6 (TRPC6) protein is a very important selective calcium channel that is closely related to the development of various cardiomyopathies. We found that the inhibition of apoptosis and proliferation of cardiomyocytes in a high-glucose environment might be closely related to the activation of the TRPC6/P-calmodulin-dependent protein kinase II pathway.