Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this stu...

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Published in:Acta pharmaceutica Sinica. B 2024-04, Vol.14 (4), p.1661-1676
Main Authors: Chen, Junhui, Zhang, Qian, Guo, Jinan, Gu, Di, Liu, Jing, Luo, Piao, Bai, Yunmeng, Chen, Jiayun, Zhang, Xinzhou, Nie, Sheng, Chen, Chunbo, Feng, Yulin, Wang, Jigang
Format: Article
Language:English
Subjects:
Diabetic nephropathy
Inflammation
Injury
Original
Oxidative stress
Proteomics
Rosmarinic acid
scRNA sequencing
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Summary:Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this study, we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels. Our results demonstrated that RA significantly alleviated renal tubular epithelial injury, particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes, while attenuating the inflammatory response of macrophages, oxidative stress, and cytotoxicity of natural killer cells. These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage, oxidative stress, and inflammation, offering valuable guidance for the clinical application of RA in the treatment of DN. Single-cell RNA sequencing (scRNA-seq) analyses have provided a novel insight into cell-specific gene expression changes in diabetic nephropathy (DP) mice with rosmarinic acid (RA) treatment. Here, this study reveals RA could reduce oxidative stress and inflammation in the PT segment and podocytes, and mitigate inflammation in M1-like macrophages and natural killer cells. This study further deepens the understanding of novel mechanisms and potential therapeutic targets of RA on DP. [Display omitted]
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2024.01.003