Astragaloside IV Downregulates β-Catenin in Rat Keratinocytes to Counter LiCl-Induced Inhibition of Proliferation and Migration.
Astragaloside IV Downregulates β-Catenin in Rat Keratinocytes to Counter LiCl-Induced Inhibition of Proliferation and Migration.
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黄芪甲苷 IV 下调大鼠角质形成细胞中的 β-连环蛋白，以对抗 LiCl 诱导的增殖和迁移抑制
DOI：
10.1155/2012/956107
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Li FL;Li X;Wang YF;Xiao XL;Xu R;Chen J;Fan B;Xu WB;Geng L;Li B
再上皮化是伤口愈合的关键步骤。传统的中药黄芪（Astragalus membranaceus，菲施）Bge用于治疗多种溃疡创面已有数百年的历史。最近的研究已经确定了这种药物中的活性化合物为黄芪甲苷IV（AS-IV），但其对角质形成细胞的治疗作用的潜在分子机制仍然知之甚少。在这项研究中，我们使用了一个体外模型的溃疡样伤口过程，氯化锂（LiCl）诱导培养的小鼠角质形成细胞，研究AS-IV治疗的影响。通过MTS/PMS比色法评价对细胞增殖的影响，通过伤口愈合划痕实验测定对细胞迁移的影响，通过流式细胞术分析对细胞周期的影响，通过免疫印迹和免疫荧光分析对蛋白质表达的影响。LiCl强烈抑制细胞增殖和迁移，上调β-catenin表达，下调增殖细胞核抗原（PCNA）表达。AS-IV处理后，细胞增殖和迁移抑制减弱，β-catenin表达明显降低，PCNA和β-tubulin表达恢复。因此，AS-IV通过调节Wnt信号通路介导小鼠角质形成细胞增殖和迁移。下调β-连环蛋白以增加角质形成细胞迁移和增殖是AS-IV可促进溃疡伤口愈合的一种机制。
Re-epithelialization is a crucial step towards wound healing. The traditional Chinese medicine, Astragalus membranaceus (Fisch) Bge, has been used for hundreds of years for many kinds of ulcerated wounds. Recent research has identified the active compound in this drug as astragaloside IV (AS-IV), but the underlying molecular mechanisms of its therapeutic action on keratinocytes remain poorly understood. In this study, we used an in vitro model of ulcer-like wound processes, lithium chloride (LiCl)-induced cultured mouse keratinocytes, to investigate the effects of AS-IV treatment. The effects on cell proliferation were evaluated by the MTS/PMS colorimetric assay, effects on cell migration were determined by a wound-healing scratch experiment, effects on the cell cycle were analyzed by flow cytometry, and effects on protein expression were analyzed by immunoblotting and immunofluorescence. LiCl strongly inhibited cell proliferation and migration, up-regulated β-catenin expression, and down-regulated proliferating cell nuclear antigen (PCNA) expression. AS-IV treatment attenuat the inhibition of proliferation and migration, significantly reducing the enhanced β-catenin expression, and recovering PCNA and β-tubulin expression. Thus, AS-IV mediates mouse keratinocyte proliferation and migration via regulation of the Wnt signaling pathway. Down-regulating β-catenin to increase keratinocyte migration and proliferation is one mechanism by which AS-IV can promote ulcerated wound healing.
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DOI：
10.1073/pnas.102657399
发表时间：
2002-05-14
影响因子：
11.1
作者：
Cheon, SS;Cheah, AYL;Alman, BA
通讯作者：
Alman, BA
影响因子：
7.3
作者：
Simka, M;Majewski, E
通讯作者：
Majewski, E
影响因子：
5.8
作者：
Rao, AS;Kremenevskaja, N;Brabant, G
通讯作者：
Brabant, G
影响因子：
5.6
作者：
WELSHONS, WV;ENGLER, KS;CURRAN, EM
通讯作者：
CURRAN, EM
影响因子：
4
作者：
Teh, Muy-Teck;Blaydon, Diana;Philpott, Michael P.
通讯作者：
Philpott, Michael P.