Cyanidin-3-glucoside upregulated NDRG2 through the PI3K/AKT pathway to alleviate EMT and ECM in renal fibrosis

Abstract Renal fibrosis is a critical progression of chronic kidney disease, and epithelial-to-mesenchymal transition (EMT) and extracellular matrix(ECM) deposition are crucial pathologic change of renal fibrosis, which still lacks of effective treatment. In this study, it was found that cyanidin-3-...

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Main Authors: Qianxue Lu, Jin Liu, Yufeng Xiong, Jun Jian, Jingsong Wang, Zhiyuan Chen, Shanshan Wan, Xiuheng Liu, Lei Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-94918-x
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Summary:Abstract Renal fibrosis is a critical progression of chronic kidney disease, and epithelial-to-mesenchymal transition (EMT) and extracellular matrix(ECM) deposition are crucial pathologic change of renal fibrosis, which still lacks of effective treatment. In this study, it was found that cyanidin-3-O-glucoside (C3G) could inhibit EMT and ECM activated by unilateral ureteral obstruction (UUO) and transforming growth factor-β1 (TGF-β1) stimulation. Moreover, N-Myc downstream-regulated gene 2(NDRG2), which involved in the progression of renal fibrosis, was down-regulated in vivo and in vitro model. However, C3G pretreatment could reverse the reductive expression of NDRG2. Furthermore, we found that the combined treatment of C3G and si-NDRG2 could reverse the decreased EMT and ECM, which induced by C3G treatment only. And the activation of Phosphatidylinositol 3-kinase (PI3K)/ Protein Kinase B (AKT) pathway significantly enhanced EMT and ECM, which was decreased by C3G treatment only in TGF-β1 induced Human Kidney 2 (HK-2) cells. In conclusion, our results demonstrated that C3G alleviated EMT and ECM by elevating NDRG2 expression through the PI3K/AKT pathway, indicating that C3G could be a potential treatment against renal fibrosis.
ISSN:2045-2322