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Upregulation of miR-21-5p rescues the inhibition of cardiomyocyte proliferation induced by high glucose through negative regulation of Rhob

Published online by Cambridge University Press:  11 December 2023

Fang Wu ,
Feng Wang ,
Qian Yang ,
Yawen Zhang ,
Ke Cai ,
Jialing Zhang Open the ORCID record for Jialing Zhang [Opens in a new window] ,
Min Xia ,
Youhua Wang ,
Xu Wang  and
Yonghao Gui
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Fang Wu
Affiliation:
Department of Neonatology, Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Feng Wang
Affiliation:
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, National Health Commission Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China Cardiovascular Center, National Health Commission Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Qian Yang
Affiliation:
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, National Health Commission Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China Cardiovascular Center, National Health Commission Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Yawen Zhang
Affiliation:
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, National Health Commission Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China Cardiovascular Center, National Health Commission Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Ke Cai
Affiliation:
Cardiovascular Center, National Health Commission Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Jialing Zhang
Affiliation:
Cardiovascular Center, National Health Commission Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai, China
Min Xia
Affiliation:
Department of Neonatology, Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Youhua Wang
Affiliation:
Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xu Wang
Affiliation:
Cancer Metabolism Laboratory, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China
Yonghao Gui*
Affiliation:
Cardiovascular Center, National Health Commission Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Qiang Li*
Affiliation:
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, National Health Commission Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
*
Corresponding authors: Y. Gui; Email: yhgui@shmu.edu.cn; Q. Li; Email: liq@fudan.edu.cn
Corresponding authors: Y. Gui; Email: yhgui@shmu.edu.cn; Q. Li; Email: liq@fudan.edu.cn
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Abstract

Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.

Keywords

MiR-21-5pmyocardial cell injuryhyperglycemiaH9c2proliferation
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 5 , October 2023 , pp. 670 - 677
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Copyright
© The Author(s), 2023. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)

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