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(+)-Catechin (CE) is mainly found in green and black tea and has many biological effects, such as anti-inflammatory, anti-cancer, anti-viral effects, protecting human organs, especially the kidney. This study aims to identify the circRNAs induced by CE in db/db mice and their roles in diabetic nephropathy progression. After the db/db mice were treated with CE, RNA-seq was performed to identify the differentially expressed circRNA and mRNAs. The ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases (Cytoscape, ClueGO, MiRWalk, STRING, et al.). Our results revealed that 6 differentially expressed circRNAs are most associated with the cholinergic synapse, neurotrophin signaling pathway, and insulin signaling pathway. Among these, circRNA.5549 and circRNA.4712 might regulate Cd36, Cyp26b1, C8a, Cyp2j13, Grem2 genes through ceRNA regulatory mechanism in the presence of CE treatment. The expanded network of proteins interacting with these 5 genes shows that the TGF-β signaling pathway, signaling pathways regulating pluripotency of stem cell, fat digestion and absorption, and PPAR signaling pathway was highly enriched. Overall, circRNA.5549 and circRNA.4712 exhibit a promotive function in CE-treated db/db mice, especially in circRNA.5549/miR-29a-5P/Cd36 regulatory network, and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.


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Identification of circRNA/miRNA/mRNA regulatory network involving (+)-catechin ameliorates diabetic nephropathy mice

Show Author's information Chao Chena,b,#Dina Zhua,b,#Shuai ZhangcWensheng Zhanga,b,d( )
Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai 519087, China
Engineering Research Center of Natural Medicine, Ministry of Education, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai 519087, China
International Cooperation Laboratory of Molecular Medicine, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization, Faculty of Geographical Science, Beijing Normal University, Beijing 100875, China

# These authors contributed equally.

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

(+)-Catechin (CE) is mainly found in green and black tea and has many biological effects, such as anti-inflammatory, anti-cancer, anti-viral effects, protecting human organs, especially the kidney. This study aims to identify the circRNAs induced by CE in db/db mice and their roles in diabetic nephropathy progression. After the db/db mice were treated with CE, RNA-seq was performed to identify the differentially expressed circRNA and mRNAs. The ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases (Cytoscape, ClueGO, MiRWalk, STRING, et al.). Our results revealed that 6 differentially expressed circRNAs are most associated with the cholinergic synapse, neurotrophin signaling pathway, and insulin signaling pathway. Among these, circRNA.5549 and circRNA.4712 might regulate Cd36, Cyp26b1, C8a, Cyp2j13, Grem2 genes through ceRNA regulatory mechanism in the presence of CE treatment. The expanded network of proteins interacting with these 5 genes shows that the TGF-β signaling pathway, signaling pathways regulating pluripotency of stem cell, fat digestion and absorption, and PPAR signaling pathway was highly enriched. Overall, circRNA.5549 and circRNA.4712 exhibit a promotive function in CE-treated db/db mice, especially in circRNA.5549/miR-29a-5P/Cd36 regulatory network, and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.

Keywords: CircRNA, Catechin, Diabetic nephropathy, miRNA, ceRNA

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Publication history

Received: 23 April 2021
Revised: 14 July 2021
Accepted: 04 August 2021
Published: 04 February 2022
Issue date: May 2022

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© 2022 Beijing Academy of Food Sciences.

Acknowledgements

Acknowledgements

This work was supported by the National Nature Science Foundation of China (81771152), National Key R&D Plan (No. 2017YFC1702500), and the Beijing Joint Project for the Central-Affiliated University (2017-01).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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