莪术醇可能通过Notch信号通路影响角质形成细胞的增殖、迁移、凋亡-东南大学学报医学版

莪术醇可能通过Notch信号通路影响角质形成细胞的增殖、迁移、凋亡

单位：保定市第二医院皮肤科, 河北保定 071051

分类号：R-33

出版年·卷·期（页码）：2023·42·第三期（339-347）

摘要：

目的: 探讨莪术醇对角质形成细胞增殖、迁移、凋亡的作用及其相关的分子机制。方法: 体外分离培养银屑病角质形成细胞,使用浓度0、10、40、80 mg·L^-1莪术醇处理细胞,CCK8实验检测细胞增殖;流式细胞术检测细胞凋亡;蛋白质印迹法检测细胞周期蛋白D1(Cyclin D1)、B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、Notch 1、Hes 1蛋白表达水平;Transwell小室、伤口愈合实验检测细胞迁移。以0 mg·L^-1莪术醇作为对照,将80 mg·L^-1莪术醇、Notch信号通路抑制剂DAPT加入80 mg·L^-1莪术醇处理的细胞内,通过上述方法检测加入Notch通路抑制剂对银屑病角质形成细胞增殖、迁移和凋亡的影响。多组间比较通过单因素方差分析,组内间比较使用LSD-t检验。结果: 莪术醇呈剂量效应降低银屑病角质形成细胞活性、迁移率、迁移细胞数和Cyclin D1、Bcl-2蛋白表达,增加凋亡率和Bax、Cleaved-Caspase3、Cleaved-Caspase9、Notch 1、Hes 1蛋白表达(P<0.05)。与莪术醇组比较,莪术醇+DAPT组细胞活性、迁移率、迁移细胞数和Cyclin D1、Bcl-2蛋白表达增加,凋亡率和Bax、Cleaved-Caspase3、Cleaved-Caspase9蛋白表达水平降低,差异有统计学意义(P<0.05)。结论: 莪术醇可能通过激活Notch信号通路抑制银屑病角质形成细胞的增殖、迁移,并诱导细胞凋亡。

Objective: To investigate the effects of curcumol on the proliferation, migration and apoptosis of keratinocytes and its related molecular mechanisms. Methods: Psoriasiskeratinocytes were isolated and cultured in vitro, treated with curcumol concentrations of 0, 10, 40, and 80 mg·L^-1, and cell counting kit(CCK8) experiment was used to detect cell proliferation; flow cytometry experiment was used to detect cell apoptosis; Western blot experiments were used to detect cyclin D1(Cyclin D1), B cell lymphoma/leukemia-2(Bcl-2), Bcl-2-related X protein(Bax), Notch 1, and Hes 1 protein expression levels; Transwell chambers and wound healing experiments were used to detect cell migration. With 0 mg·L^-1 curcumol as control, 80 mg·L^-1 curcumol and Notch signaling pathway inhibitor DAPT were added into the cells treated with 80 mg·L^-1 curcumol, and the effects of adding Notch pathway inhibitors on the proliferation, migration and apoptosis of psoriasis keratinocytes were detected by the above method. Comparisons among multiple groups were performed by one-way ANOVA, and LSD-t was used for within-group comparison. Results: Curcumol decreased keratinocyte activity, migration rate, number of migrating cells, Cyclin D1, Bcl-2 protein expression, and increased apoptosis rate and expression of Bax, Cleaved-Caspase3, Cleaved-Caspase9, Notch 1, Hes 1 protein in psoriasis with a dose-dependent manner(P<0.05). Compared with the curcumol group, the cell activity, migration rate, number of migrated cells, and expression of Cyclin D1 and Bcl-2 proteins in the curcumol+DAPT group increased, while the apoptosis rate and Bax, Cleaved-Caspase3, Cleaved-Caspase9 protein expression levels decreased, with a statistically significant difference(P<0.05). Conclusion: Curcumol may inhibit the proliferation and migration of psoriatic keratinocytes and induce cell apoptosis by activating Notch signaling pathway.

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