Transcriptomic and proteomic investigation of the ameliorative effect of total polyphenolic glycoside extract on hepatic fibrosis in Lamiophlomis rotata Kudo via the AGE/RAGE pathway
文献类型：期刊论文
| 作者 | Yang, Congwen; Geng, Xiaoyu; Wan, Guoguo; Song, Liang; Wang, Ying; Zhou, Guoying ; Wang, Jianwei; Pan, Zheng
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| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
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| 出版日期 | 2024 |
| 卷号 | 324 |
| 英文摘要 | Ethnopharmacological relevance: During the regression of liver fibrosis, a decrease in hepatic stellate cells (HSCs) can occur through apoptosis or inactivation of activated HSCs (aHSCs). A new approach for antifibrotic therapy involves transforming hepatic myofibroblasts into a quiescent-like state. Lamiophlomis rotata (Benth.) Kudo (L. rotata), an orally available Tibetan herb, has traditionally been used to treat skin disease, jaundice, and rheumatism. In our previous study, we found that the total polyphenolic glycoside extract of L. rotata (TPLR) promotes apoptosis in aHSCs for the treatment of hepatic fibrosis. However, whether TPLR induces aHSCs to become inactivated HSCs (iHSCs) is unclear, and the underlying mechanism remains largely unknown. Purpose: This study aimed to examine the impact of TPLR on the phenotypes of hepatic stellate cells (HSCs) during the regression of liver fibrosis and explore the potential mechanism of action. Methods: The effect of TPLR on the phenotypes of hepatic stellate cells (HSCs) was assessed using immunofluorescence (IF) staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting. Transcriptomic and proteomic methods were employed to identify the main signaling pathways involved. Based on the omics results, the likely mechanism of TPLR on the phenotypes of aHSCs was confirmed through overexpression and knockdown experiments in TGF-beta 1-activated LX-2 cells. Using a CCl4-induced liver fibrosis mouse model, we evaluated the anti-hepatic fibrosis effect of TPLR and explored its potential mechanism based on omics findings. Results: TPLR was found to induce the differentiation of aHSCs into iHSCs by significantly decreasing the protein expression of alpha-SMA and Desmin. Transcriptomic and proteomic analyses revealed that the AGE/RAGE signaling pathway plays a crucial role in the morphological transformation of HSCs following TPLR treatment. In vitro experiments using RAGE overexpression and knockdown demonstrated that the mechanism by which TPLR affects the phenotype of HSCs is closely associated with the RAGE/RAS/MAPK/NF-kappa B axis. In a model of liver fibrosis, TPLR obviously inhibited the generation of AGEs and alleviated liver tissue damage and fibrosis by downregulating RAGE and its downstream targets. Conclusion: The AGE/RAGE axis plays a pivotal role in the transformation of activated hepatic stellate cells (aHSCs) into inactivated hepatic stellate cells (iHSCs) following TPLR treatment, indicating the potential of TPLR as a therapeutic agent for the management of liver fibrosis. |
| 源URL | [http://210.75.249.4/handle/363003/62105]  |
| 专题 | 西北高原生物研究所_中国科学院西北高原生物研究所 |
| 推荐引用方式 GB/T 7714 | Yang, Congwen,Geng, Xiaoyu,Wan, Guoguo,et al. Transcriptomic and proteomic investigation of the ameliorative effect of total polyphenolic glycoside extract on hepatic fibrosis in Lamiophlomis rotata Kudo via the AGE/RAGE pathway[J]. JOURNAL OF ETHNOPHARMACOLOGY,2024,324. |
| APA | Yang, Congwen.,Geng, Xiaoyu.,Wan, Guoguo.,Song, Liang.,Wang, Ying.,...&Pan, Zheng.(2024).Transcriptomic and proteomic investigation of the ameliorative effect of total polyphenolic glycoside extract on hepatic fibrosis in Lamiophlomis rotata Kudo via the AGE/RAGE pathway.JOURNAL OF ETHNOPHARMACOLOGY,324. |
| MLA | Yang, Congwen,et al."Transcriptomic and proteomic investigation of the ameliorative effect of total polyphenolic glycoside extract on hepatic fibrosis in Lamiophlomis rotata Kudo via the AGE/RAGE pathway".JOURNAL OF ETHNOPHARMACOLOGY 324(2024). |
入库方式： OAI收割
来源：西北高原生物研究所
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