Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells.
Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells.
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DOI：
10.1186/s40360-018-0255-9
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发表时间：
2018-10-16
影响因子：
2.9
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Lv J;Bai R;Wang L;Gao J;Zhang H
越来越多的研究正在调查中医药对肝纤维化的影响，但只有少数研究探讨了青蒿琥酯（ART）的抗纤维化特性。本研究旨在探讨ART对人肝星状细胞系LX-2细胞的抗肝纤维化作用，并通过黏着斑激酶（FAK）/蛋白激酶B（Akt）/ β-catenin途径探讨其可能的分子机制。用不同浓度的ART（0、12.5、25和50 μg/ml）刺激LX-2细胞12、24、48和72 h，采用CCK-8法检测细胞增殖情况。用不同剂量的ART处理LX-2细胞（0、12.5、25和50 μg/ml）作用24 h后，用流式细胞仪检测细胞凋亡，使用逆转录-定量聚合酶链反应（RT-qPCR）测定编码I型胶原或α-平滑肌肌动蛋白（α-SMA）的mRNA水平，并测定FAK/Akt/β-SMA中关键蛋白的水平。通过蛋白质印迹法评估连环蛋白信号通路。将FAK的特异性抑制剂添加到LX-2细胞培养物中以探索潜在的信号传导。ART能有效抑制LX-2细胞的增殖，并呈剂量依赖性地促进细胞的早期凋亡，同时显著下调α-SMA和I型胶原的mRNA表达。此外，ART与FAK抑制剂PF 562271相似，通过降低磷酸化FAK、Akt和GSK-3β的水平，显著抑制FAK/Akt/β-catenin信号通路。本研究表明ART可调节LX-2的增殖、凋亡和活化。ART的抗纤维化机制与FAK/Akt/β-catenin通路有关。未来的研究应该验证和扩展这些发现，并探索其他分子，从而作为有用的治疗靶点。
An increasing number of studies are investigating the effects of Chinese medicine on hepatic fibrosis, but only few studies have examined the anti-fibrogenic properties of Artesunate (ART). The aim of the present study was to explore the anti-fibrotic effects of ART on LX-2 cells, the human HSC cell line, and to determine potential molecular mechanisms via the focal adhesion kinase (FAK)/ protein kinase B (Akt)/ β-catenin pathway. LX-2 cells were stimulated with different concentration of ART (0, 12.5, 25 and 50 μg/ml) for 12, 24, 48 or 72 h, their proliferation was analyzed using the Cell Counting Kit-8 (CCK-8) assay. LX-2 cells were treated with different doses of ART (0, 12.5, 25 and 50 μg/ml) for 24 h, their apoptosis was measured using flow cytometry, the levels of mRNAs encoding collagen I or α-smooth muscle actin (α-SMA) were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the levels of key proteins in the FAK/Akt/β-catenin signaling pathway were assessed by western blotting. Specific inhibitors of FAK were added to the LX-2 cells cultures to explore the potential signaling. Exposing LX-2 cells to ART efficiently inhibited their proliferation, significantly promoted early apoptosis in a dose-dependent manner, and markedly downregulated the mRNA expression of α-SMA and collagen I. In addition, ART, similar to FAK inhibitor PF562271 significantly inhibited the FAK/Akt/β-catenin signaling pathway by reducing the levels of phosphorylated FAK, Akt and GSK-3β. Our present study shows that ART could regulate the proliferation, apoptosis and activation of LX-2. Meanwhile, the anti-fibrogenic mechanisms of ART was correlated with FAK/Akt/β-catenin pathway. Future research should verify and extend these findings, as well as explore other molecules and therefore serve as useful therapeutic targets.
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影响因子：
3.3
作者：
Cui, Lei;Jia, Xin;Zhu, Huixia
通讯作者：
Zhu, Huixia
影响因子：
3.4
作者：
Ge WS;Wang YJ;Wu JX;Fan JG;Chen YW;Zhu L
通讯作者：
Zhu L
DOI：
10.3390/molecules20011277
发表时间：
2015-01-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lee PJ;Woo SJ;Jee JG;Sung SH;Kim HP
通讯作者：
Kim HP
影响因子：
13.5
作者：
Kamo, Naoko;Ke, Bibo;Busuttil, Ronald W.;Kupiec-Weglinski, Jerzy W.
通讯作者：
Kupiec-Weglinski, Jerzy W.
影响因子：
3.6
作者：
Xu N;Zhou X;Wang S;Xu LL;Zhou HS;Liu XL
通讯作者：
Liu XL