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

作者全名："Yang, Congwen; Geng, Xiaoyu; Wan, Guoguo; Song, Liang; Wang, Ying; Zhou, Guoying; Wang, Jianwei; Pan, Zheng"

作者地址："[Yang, Congwen; Geng, Xiaoyu; Wan, Guoguo; Song, Liang; Wang, Ying; Wang, Jianwei; Pan, Zheng] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing, Peoples R China; [Yang, Congwen; Song, Liang; Wang, Jianwei; Pan, Zheng] Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing, Peoples R China; [Zhou, Guoying] Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Qinghai Tibet Plateau Biol Re, Xining 810008, Peoples R China; [Pan, Zheng] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing, Peoples R China"

通信作者："Pan, Z (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing, Peoples R China."

来源：JOURNAL OF ETHNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001175329900001

JCR分区：Q1

影响因子：5.4

年份：2024

卷号：324

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Proteomics and transcriptomic; AGE/RAGE; Polyphenolic glycosides; Hepatic fibrosis; Lamiophlomis rotata

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."

基金机构：National Natural Science Foundation of China [81973567]; Chongqing Municipal Education Commission Foundation [KJZD-K202215104]; Chongqing Commission of Science and Technology [cstc2022ycjh bgzxm0010]

基金资助正文："This work was supported by the National Natural Science Foundation of China (81973567) , Chongqing Municipal Education Commission Foundation (KJZD-K202215104) , and Chongqing Commission of Science and Technology (cstc2022ycjh bgzxm0010) ."