首页|基于内质网应激PERK-ATF4-CHOP信号通路探究姜黄素对人增生性瘢痕成纤维细胞的影响及作用机制

基于内质网应激PERK-ATF4-CHOP信号通路探究姜黄素对人增生性瘢痕成纤维细胞的影响及作用机制

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目的 基于内质网应激PERK-ATF4-CHOP信号通路探究姜黄素(curcumin,Cur)对人增生性瘢痕成纤维细胞(human hypertrophic scar fibroblasts,HSFbs)的影响及其作用机制.方法 选取自 2022 年 2月至 2023 年 3 月,新疆医科大学第一附属医院整形美容外科就诊的 6 例增生性瘢痕患者,获取其增生性瘢痕组织,经体外培养增生性瘢痕成纤维细胞;通过CCK-8实验法检测不同浓度的Cur对HSFbs细胞增殖活性的影响,根据增殖活性结果数据分析后将实验分为空白组、1/2 半抑制浓度(IC50)组、IC50 组;EDU检测细胞增殖能力;流式细胞术检测Cur干预后各组细胞的凋亡能力;流式细胞术检测Cur作用 24h后细胞周期的影响;划痕实验检测Cur作用 24h后细胞的迁移能力;Western blot检测Cur作用 24h后细胞中与内质网应激相关蛋白ATF4、CHOP、Cleaved-Caspase-12 表达.结果 随着Cur药物浓度的逐渐增高,HSFbs的细胞增殖活性逐渐降低,且呈现出明显的浓度依赖性,其IC50 值为 71.33 μmol/L;细胞周期实验中Cur干预HSFbs 24 h后,将大多数的HSFbs阻滞在G1 期;实验分组的Cur干预 24h后显著减弱了HSFbs的迁移能力;显著促进了HSFbs的凋亡;Western blot实验后结果数据显示,Cur可以显著上调细胞中ATF4、CHOP、Cleaved-Caspase-12 的蛋白表达水平.结论 Cur可通过激活内质网应激PERK-ATF4-CHOP信号通路调节相关蛋白,抑制HSFbs细胞增殖及迁移,促进HSFbs细胞凋亡.
Effects of curcumin on human hypertrophic scar fibroblasts and its mechanism based on endoplasmic reticulum stress PERK-ATF4-CHOP signaling pathway
Objective To investigate the effect of curcumin(Cur)on human hypertrophic scar fibroblasts(HSFbs)and its mecha-nism based on endoplastic stress of the PERK-ATF4-CHOP signal network.Methods From February 2022 to March 2023,patients who received plastic surgery treatment from the First Affiliated Hospital of Xinjiang Medical University were studied.Their hypertrophic scar tissue was obtained and human hypertrophic scar fibroblasts were cultured in vitro.The effect of different concertration Cur on the cell pro-liferation activity of HSFbs was measured by CCK-8 assay.According to the analysis of proliferative activity data,the experiment was di-vided into blank group,1/2 IC50 group,and IC50 group.Detection of cell proliferation activity using EDU method.Flow cytometry was used to detect the apoptosis ability of cells in each group after Cur intervention.The effect of Cur on cell cycle was detected by flow cytome-try after 24 hours of treatment.Scrscratch assto detect cell invasion and migration ability.Western blot Expression of the ER stress-related proteins PERK,ATF 4,CHOP,and Cleaved-Caspase-12 in the cells.Results As the concentration of Cur gradually increases,the cell survival rate of HSFbs gradually decreased and showed concentration dependence,with an IC50 value of 71.33 μmol/L.After the action of Cur on HSFbs24h,HSFbs was arrested in G1 phase.Cur intervention in the experimental group significantly inhibited the migration ability of HSFbs after 24 hours.The apoptosis of HSFbs was significantly promoted.Western blot experiment showed that Cur can significantly upregulate the protein expression level of PERK,ATF 4,CHOP and Cleaved-Caspase-12 in cells.Conclusion Cur can activate Endo-plasmic reticulum stress PERK-ATF4-CHOP signaling pathway,inhibit cell proliferation and migration of HSFbs,and promote cell apop-tosis of HSFbs.

Endoplasmic reticulum stressPERK-ATF 4-CHOP signaling pathwayCurcuminHuman hypertrophic scar fi-broblasts

齐郁松、卜盼盼、赵皎均、田文融、马少林

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新疆医科大学第一附属医院 整形美容外科,新疆 乌鲁木齐 830011

内质网应激 PERK-ATF4-CHOP信号通路 姜黄素 人增生性瘢痕成纤维细胞

国家自然科学基金地区基金

81760345

2024

中国美容整形外科杂志
中国医师协会 辽宁省人民医院 沈阳军区总医院

中国美容整形外科杂志

CSTPCD
影响因子:0.605
ISSN:1673-7040
年,卷(期):2024.35(2)
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