炎症体
肝星状细胞
四氯化碳
纤维化
受体
吡喃结构域
化学
肝纤维化
雌激素受体
四氯化碳
内分泌学
信号转导
内科学
癌症研究
细胞生物学
生物
医学
有机化学
癌症
乳腺癌
作者
Liubing Lin,Mengen Zhou,Renye Que,Yirong Chen,Xiaolin Liu,Kehui Zhang,Zhe Shi,Yong Li
标识
DOI:10.1139/bcb-2020-0561
摘要
Liver fibrosis is the most common pathway in most types of chronic liver damage, characterized by an imbalance of ECM degradation and synthesis. Saikosaponin-d (SSd) possesses anti-inflammatory and anti-fibrotic effects. However, the underlying mechanism by which SSd represses hepatic stellate cell (HSC) activation remains unclear. Here, we found that SSd remarkably alleviated carbon tetrachloride (CCl4)-induced liver fibrosis, as evidenced by decreased collagen levels and profibrotic marker (COl1a1 and α-smooth muscle actin (SMA)) expression. SSd repressed CCl4-induced NOD-like receptor family pyrin-domain-containing-3 (NLRP3) activation in fibrotic livers, as suggested by decreased levels of NLRP3, IL-18, and IL-β. The primary HSCs of CCl4 mice exhibited a significant increase in profibrotic marker expression and NLRP3 activation, but SSd treatment reversed this effect. SSd also repressed TGF-β-induced profibrotic marker expression and NLRP3 activation in vitro. Mechanistically, TGF-β decreased the expression of estrogen receptor-β (ERβ) in HSCs, whereas SSd treatment reversed this effect. ERβ inhibition enhances NLRP3 activation in HSCs. More importantly, ERβ or NLRP3 inhibition partially destroyed the function of SSd in liver fibrosis. In summary, the current data suggest that SSd prevents hepatic fibrosis by regulating the ERβ/NLRP3 inflammasome pathway and suggests SSd as a potential agent for treating liver fibrosis.
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