EGCG suppressed activation of hepatic stellate cells by regulating the PLCE1/IP3/Ca2+ pathway.
(-)-Epigallocatechin-3-O-gallate (EGCG), one of the green tea catechins, exhibits significant antioxidant properties that play an essential role in various diseases. However, the functional role and underlying mechanism of EGCG in stimulating of hepatic stellate cells (HSCs) remain unexplored in tra...
| Publicado en: | European Journal of Nutrition Vol. 63; no. 8; pp. 3255 - 3269 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Dec2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=180549921&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 180549921 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14366207 CR0 jtl: European Journal of Nutrition issn: 14366207 maglogo: N pubinfo: dt: Dec2024 vid: 63 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 180549921 179921643 180549921 180549921 10.1007/s00394-024-03504-w 180549921 ppf: 3255 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: EGCG suppressed activation of hepatic stellate cells by regulating the PLCE1/IP3/Ca2+ pathway. aug: au: Lin, Ying Zhang, Yan Li, Yang Xu, Qihan Zhang, Yijie Chen, Tingting Wang, Jun Li, Jierui Gong, Jiacheng Chen, Zhuoer Yang, Qiaomu Li, Xu affil: Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, No. 1838, North of Guangzhou Avenue, 510515, Guangzhou City, Guangdong Province, China sug: subj: Liver Cirrhosis Drug Therapy Flavonoids Pharmacodynamics Green Tea Pharmacodynamics Cell Line Drug Effects Phospholipases Metabolism Calcium Metabolism Signal Transduction Drug Effects Hydrocarbons, Chlorinated Adverse Effects Administration, Oral Gene Expression Profiling Antioxidants Green Tea Administration and Dosage Animal Studies China Mice In Vitro Studies Sequence Analysis Inositol Phosphates Metabolism Cell Proliferation Cell Movement Reactive Oxygen Species Transcription Factors Descriptive Statistics ab: (-)-Epigallocatechin-3-O-gallate (EGCG), one of the green tea catechins, exhibits significant antioxidant properties that play an essential role in various diseases. However, the functional role and underlying mechanism of EGCG in stimulating of hepatic stellate cells (HSCs) remain unexplored in transcriptomics sequencing studies. The present study suggests that oral administration of EGCG at a dosage of 200 mg/kg/day for a duration of four weeks exhibits significant therapeutic potential in a murine model of liver fibrosis induced by CCl4. The activation of HSCs in vitro was dose-dependently inhibited by EGCG. The sequencing analysis data reveled that EGCG exerted a regulatory effect on the calcium signal in mouse HSCs, resulting in a decrease in calcium ion concentration. Further analysis revealed that EGCG inhibited the expression of phospholipase C epsilon-1 (PLCE1) and inositol 1, 4, 5-trisphosphate (IP3) in activated mouse HSCs. Additionally, EGCG contributes to the reduction the concentration of calcium ions by regulating PLCE1. After the knockdown of PLCE1, free calcium ion concentrations decreased, resulting in the inhibition of both cell proliferation and migration. Interestingly, the expression of PLCE1 and cytosolic calcium levels were regulated by reactive oxygen species(ROS). Furthermore, our findings suggest that ROS might inhibit the expression of PLCE1 by inhibiting TFEB, a transcription activator involved in the nuclear translocation process. Our study provided novel evidence regarding the regulatory effects of EGCG on activated HSCs (aHSCs) in mice by the calcium signaling pathway, emphasizing the crucial role of PLCE1 within the calcium signaling network of HSCs. The proposition was also made that PLCE1 holds promise as a novel therapeutic target for murine liver fibrosis. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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