EGCG suppressed activation of hepatic stellate cells by regulating the PLCE1/IP3/Ca2+ pathway.

Autor:	Lin, Ying, Zhang, Yan, Li, Yang, Xu, Qihan, Zhang, Yijie, Chen, Tingting, Wang, Jun, Li, Jierui, Gong, Jiacheng, Chen, Zhuoer, Yang, Qiaomu, Li, Xu
Předmět:	CALCIUM metabolism IN vitro studies CIRRHOSIS of the liver FLAVONOIDS GREEN tea HYDROCARBONS CELL proliferation CELLULAR signal transduction ORAL drug administration CELL motility TRANSCRIPTION factors DESCRIPTIVE statistics CELL lines MICE INOSITOL phosphates REACTIVE oxygen species PHOSPHOLIPASES GENE expression profiling ANTIOXIDANTS ANIMAL experimentation SEQUENCE analysis
Zdroj:	European Journal of Nutrition; Dec2024, Vol. 63 Issue 8, p3255-3268, 14p
Abstrakt:	(-)-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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink