Artesunate treatment ameliorates ultraviolet irradiation-driven skin photoaging via increasing β-catenin expression.
Artesunate treatment ameliorates ultraviolet irradiation-driven skin photoaging via increasing β-catenin expression.
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青蒿琥酯治疗通过增加β-连环蛋白表达改善紫外线照射驱动的皮肤光老化
DOI：
10.18632/aging.203749
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发表时间：
2021-12-09
期刊：
影响因子：
--
通讯作者：
Zong S
中科院分区：
文献类型：
--
作者：
Tian L;Ke D;Hong Y;Zhang C;Tian D;Chen L;Zhan L;Zong S
目的：青蒿素的半合成衍生物青蒿琥酯具有多种药理活性。然而，Art对皮肤光老化的影响尚不清楚。在此，我们研究了Art是否能改善紫外线照射下HaCaT细胞和小鼠的皮肤光老化。方法：采用紫外线（UVB, 20mJ/cm2）照射HaCaT细胞5 d，构建皮肤光老化细胞模型。用3种浓度的Art（1、5和20 μg/ml）预处理HaCaT细胞，每天2 h。5 d后，检测HaCaT细胞衰老、ROS生成、SOD水平、p16INK4a和β-catenin表达、增殖和凋亡情况。观察Art对正常细胞的影响。转染sh-β-catenin或XAV-939后，用20 μg/ml Art预处理HaCaT细胞，并用UVB照射。5 d后观察皮肤光老化。建立皮肤光老化小鼠模型，探讨Art和β-catenin沉默对皮肤光老化的影响。结果：Art处理抑制UVB照射HaCaT细胞衰老、细胞内ROS生成、p16INK4a表达和凋亡，促进增殖、SOD和β-catenin表达。但是Art对正常细胞没有毒性作用。sh-β-catenin或XAV-939沉默β-catenin会加剧UVB照射介导的HaCaT细胞衰老、凋亡和ROS产生，Art处理可改善这一现象。在小鼠模型中也证实了Art对皮肤光老化的治疗作用。结论：上述结果提示Art治疗通过增强β-catenin的表达来缓解UVB照射引起的皮肤光老化，为Art的药理作用提供了新的线索。
Objective: Artesunate, a semi-synthetic derivative of artemisinin, exerts various pharmacological activities. Nevertheless, the effects of Art on skin photoaging remain unclear. Herein, we investigated whether Art ameliorated ultraviolet-irradiated skin photoaging in HaCaT cells and mice. Methods: To construct skin photoaging cellular models, HaCaT cells were irradiated by UV (UVB, 20mJ/cm2) for 5 days. HaCaT cells were pretreated with three concentrations of Art (1, 5 and 20 μg/ml) for 2 h each day. After 5 days, cell senescence, ROS production, SOD levels, p16INK4a and β-catenin expression, proliferation and apoptosis were detected in HaCaT cells. Effects of Art on normal cells were investigated. After sh-β-catenin transfection or XAV-939 treatment, HaCaT cells were pretreated with 20 μg/ml Art and irradiated by UVB. After 5 days, skin photoaging was then observed. Furthermore, skin photoaging mouse models were established and the effects of Art and β-catenin silencing on skin photoaging were investigated. Results: Art treatment suppressed cell senescence, intracellular ROS production, p16INK4a expression and apoptosis and promoted proliferation and SOD and β-catenin expression in UVB irradiated HaCaT cells. But Art had no toxic effects on normal cells. Silencing β-catenin by sh-β-catenin or XAV-939 exacerbated UVB irradiation-mediated cell senescence, apoptosis, and ROS production in HaCaT cells, which was ameliorated by Art treatment. The therapeutic effects of Art on skin photoaging were also confirmed in mouse models. Conclusions: These findings suggested that Art treatment alleviated UVB irradiation-driven skin photoaging through enhancing β-catenin expression, which offered novel clues for pharmacological activity of Art.
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影响因子：
--
作者：
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DOI：
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