Molecular mechanism of Xinyang Tablets in improving myocardial fibrosis in uremic cardiomyopathy based on single-cell sequencing technology.
10.19540/j.cnki.cjcmm.20240730.401
- Author:
Shi-Hao NI
1
;
Zi-Ru LI
1
;
Si-Jing LI
1
;
Xing-Ling HE
1
;
Jin LI
2
;
Xing-Ling CHEN
2
;
Wen-Jie LONG
3
;
Wei-Wei ZHANG
4
;
Hui-Li LIAO
3
;
Lu LU
2
;
Zhong-Qi YANG
5
Author Information
1. State Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Lingnan Medical Research Center, Guangzhou University of Chinese Medicine Guangzhou 510405, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
2. Lingnan Medical Research Center, Guangzhou University of Chinese Medicine Guangzhou 510405, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
3. Geriatrics Department, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
4. Shenzhen Bao'an Traditional Chinese Medicine Hospital Group Shenzhen 518133, China.
5. State Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Geriatrics Department, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Lingnan Medical Research Center, Guangzhou University of Chinese Medicine Guangzhou 510405, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
- Publication Type:Journal Article
- Keywords:
Xinyang Tablets;
myocardial fibrosis;
osteopontin;
single-cell sequencing;
uremic cardiomyopathy
- MeSH:
Animals;
Drugs, Chinese Herbal/administration & dosage*;
Mice;
Cardiomyopathies/pathology*;
Single-Cell Analysis;
Male;
Fibrosis/drug therapy*;
Myocardium/metabolism*;
Uremia/metabolism*;
Tablets;
Mice, Inbred C57BL;
Humans
- From:
China Journal of Chinese Materia Medica
2024;49(24):6746-6754
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the ameliorative effect of Xinyang Tablets on myocardial fibrosis in uremic cardiomyopathy(UCM) using single-cell sequencing technology. UCM mouse models were established by 5/6 nephrectomy(NPM) and randomly divided into the model group, Xinyang Tablets group, and sham-operated(sham) group as the control. The Xinyang Tablets group received postoperative interventions of Xinyang Tablets(0.34 g·kg~(-1)). After eight weeks, the hearts of the mice in each group were disassociated and subjected to 10×Genomics single-cell sequencing. The data were subjected to t-SNE dimensionality reduction, K-means clustering, and CellMarker annotation prior to analyzing differential expression and cell differentiation trajectories using the Seurat and Monocle3 tools. Additionally, the CellChat tool was used to parse intercellular signaling communication. The results showed that a total of nine types of cells including fibroblasts, endothelial cells, and immune cells were identified in this study. The single-cell expression results of fibroblasts and Gene Ontology(GO) enrichment analysis showed that Xinyang Tablets regulated myocardial fibrosis factors and related signals. Mimetic timing analysis identified three major differentiation trajectories of mouse cardiac fibroblasts and identified the expression of secreted phosphoprotein 1(Spp1) as consistent with the fibroblast differentiation trajectory. Cellular interaction network analysis showed that the communication signals between mouse cardiac fibroblasts and other cells were weakened in the Xinyang Tablets group compared with the model group. The results of ligand-receptor interaction analysis showed that the interaction between myeloid cell-derived osteopontin(OPN) and cardiac fibroblasts and between myeloid cell Spp1 ligand and cardiac fibroblast receptor of mice in the Xinyang Tablets group was weakened compared with the model group. In conclusion, Xinyang Tablets may improve myocardial fibrosis in UCM by inhibiting both endogenous and exogenous OPN at the single-cell level.
