Phillygenin 抑制 TGF-β1 诱导的肝星状细胞活化和炎症:Bax/Bcl-2 和 Wnt/β-catenin 通路的调控。

IF 4.5 2区 医学 Q2 CELL BIOLOGY Inflammation Pub Date : 2024-08-01 Epub Date: 2024-02-23 DOI:10.1007/s10753-024-01984-w
Cheng Wang, Shenglin Zhang, Yanzhi Li, Lihong Gong, Chenhao Yao, Ke Fu, Yunxia Li
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引用次数: 0

摘要

肝纤维化(HF)是肝硬化和肝细胞癌的前兆,由肝脏中结缔组织的异常增殖和细胞外基质的过度积累引起。值得注意的是,肝星状细胞(HSCs)的活化是导致肝纤维化的关键环节。连翘素(PHI,C21H24O6)是从传统中药连翘中提取的木质素成分,具有抗炎、抗氧化和抗肿瘤等多种药理活性。然而,PHI 能否直接抑制造血干细胞活化并改善高频的作用机制尚未完全阐明。因此,本研究旨在探讨 PHI 的体外抗 HF 作用及其分子机制。以转化生长因子-β1(TGF-β1)激活的小鼠造血干细胞(mHSCs)和人造血干细胞(LX-2 细胞)为 HF 体外模型,用不同浓度的 PHI 处理 24 小时。随后,在显微镜下观察细胞形态学变化,用MTT法分析细胞活力,用流式细胞术检测细胞周期和细胞凋亡,并用免疫荧光、ELISA、RT-qPCR和Western blot等方法探讨PHI抗纤维化作用的机制。结果表明,PHI能抑制TGF-β1激活的mHSCs和LX-2细胞的增殖,使细胞周期停滞在G0/G1期,降低激活的mHSCs和LX-2细胞中α-SMA、胶原蛋白I、TIMP1和MMP2基因及蛋白的水平,促进细胞凋亡。此外,PHI 还能减少活化的 mHSCs 和 LX-2 细胞中炎症因子的表达,这表明它具有潜在的抗炎作用。从机理上讲,PHI至少部分通过调节Bax/Bcl-2和Wnt/β-catenin通路抑制了TGF-β1诱导的造血干细胞活化和炎症。总之,PHI 具有显著的抗心房颤动作用,可能是一种治疗心房颤动的有前途的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Phillygenin Inhibits TGF-β1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/β-catenin Pathways.

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-β1 (TGF-β1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-β1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-β1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/β-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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