Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Xiaoyao San restores NK cell anti-fibrotic activity through regulation of EZH2 in liver fibrosis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chen Qingqing, Wang Jia, Guo Dong, Kou Fang, Cai Hong, Zheng Guangyong, Lu Yiyu
Аннотация
BACKGROUND: Liver fibrosis poses a major global health issue, with few effective treatments currently available. Natural killer (NK) cells possess the capability to target activated hepatic stellate cells (HSCs) via their activating receptors, such as natural killer group 2 member D (NKG2D) and natural killer p46. Nonetheless, the fibrotic environment often limits their effectiveness in tackling fibrosis. Although the functions of Enhancer of zeste homolog 2 (EZH2) in the activation of HSCs and the regulation of NK cells are established, its influence on NK cell-driven anti-fibrotic activities in liver fibrosis, along with the mechanisms by which the traditional Chinese remedy Xiaoyao San (XYS) demonstrates its anti-fibrotic properties, remain to be fully clarified.
PURPOSE: This study aims to investigate whether EZH2 suppresses NK cell anti-fibrotic function by reducing NK cell abundance, maturation, and activation, and to evaluate whether XYS restores NK cell-mediated elimination of activated HSCs through EZH2 inhibition.
METHODS: We established carbon tetrachloride-induced liver fibrosis in mice with NK cell-specific conditional knockout of Ezh2 and mice with hepatocyte-specific overexpression of Ezh2 with or without XYS intervention. In vitro co-culture experiments using LX-2 and NK92MI cells were performed to dissect direct effects of XYS on EZH2 expression and NK cell cytotoxicity. Liver fibrosis was assessed by histology, serum biochemistry, and Western blot. NK cell abundance, maturation, and NKG2D expression were examined through flow cytometry. Both bulk and single-cell RNA sequencing were conducted to characterize transcriptomic alterations.
RESULTS: NK cell-specific deletion of Ezh2 attenuated carbon tetrachloride-induced fibrosis, increased hepatic NK cell proportion and the abundance of mature CD11b⁺ NK subsets, and altered NK cell effector gene expression. Conversely, hepatocyte-specific overexpression of Ezh2 exacerbated fibrosis, reduced NK cell abundance, impaired maturation, and suppressed NKG2D expression. XYS treatment partially reversed these effects, reduced EZH2 and fibrogenic marker expression, and enhanced NK92MI-mediated cytotoxicity against LX-2 cells in vitro.
CONCLUSION: EZH2 acts as an intrinsic suppressor of NK cell anti-fibrotic activity in liver fibrosis. XYS restores NK cell function through EZH2 inhibition, providing a mechanistic basis for its therapeutic application in chronic liver fibrosis.
PURPOSE: This study aims to investigate whether EZH2 suppresses NK cell anti-fibrotic function by reducing NK cell abundance, maturation, and activation, and to evaluate whether XYS restores NK cell-mediated elimination of activated HSCs through EZH2 inhibition.
METHODS: We established carbon tetrachloride-induced liver fibrosis in mice with NK cell-specific conditional knockout of Ezh2 and mice with hepatocyte-specific overexpression of Ezh2 with or without XYS intervention. In vitro co-culture experiments using LX-2 and NK92MI cells were performed to dissect direct effects of XYS on EZH2 expression and NK cell cytotoxicity. Liver fibrosis was assessed by histology, serum biochemistry, and Western blot. NK cell abundance, maturation, and NKG2D expression were examined through flow cytometry. Both bulk and single-cell RNA sequencing were conducted to characterize transcriptomic alterations.
RESULTS: NK cell-specific deletion of Ezh2 attenuated carbon tetrachloride-induced fibrosis, increased hepatic NK cell proportion and the abundance of mature CD11b⁺ NK subsets, and altered NK cell effector gene expression. Conversely, hepatocyte-specific overexpression of Ezh2 exacerbated fibrosis, reduced NK cell abundance, impaired maturation, and suppressed NKG2D expression. XYS treatment partially reversed these effects, reduced EZH2 and fibrogenic marker expression, and enhanced NK92MI-mediated cytotoxicity against LX-2 cells in vitro.
CONCLUSION: EZH2 acts as an intrinsic suppressor of NK cell anti-fibrotic activity in liver fibrosis. XYS restores NK cell function through EZH2 inhibition, providing a mechanistic basis for its therapeutic application in chronic liver fibrosis.