芦荟大黄素通过血小板凝血酶蛋白-1-PI3k-Akt通路抑制瘢痕组织纤维化的研究
Aloe-emodin inhibits scar tissue fibrosis through thrombospondin-1-PI3k-Akt pathway
作者:耿红宝, 张星懿, 周思玮, 李娜, 刘佳, 苑学微, 宁春柳, 张旭东, 黄威
Author:Geng Hongbao, Zhang Xingyi, Zhou Siwei, Li Na, Liu Jia, Yuan Xuewei, Ning Chunliu, Zhang Xudong, Huang Wei
收稿日期:2024-11-17 年卷(期)页码:2025,43(5):636-636-647
期刊名称:华西口腔医学杂志
Journal Name:West China Journal of Stomatology
关键字:芦荟大黄素,血小板凝血酶蛋白-1,PI3K-Akt信号通路,纤维化,腭部瘢痕,
Key words:aloe-emodin,thrombospondin-1,PI3K-Akt signaling pathway,fibrosis,palatal scar,
基金项目:河北省医学科学研究课题计划(20240510)
中文摘要
目的 探讨芦荟大黄素通过血小板凝血酶蛋白-1(THBS1)—磷脂酰肌醇3-激酶(PI3K)—蛋白激酶B(Akt)抑制瘢痕组织纤维化的机制。 方法 对人腭裂术后瘢痕组织来源成纤维细胞进行培养,采用不同浓度(10、20、30、40、50 μmol/L)芦荟大黄素作用于该细胞并检测其细胞活性,同时对瘢痕组织及细胞进行转录组测序,采用生物信息学方法挖掘瘢痕组织纤维化的潜在靶点及信号通路。 结果 芦荟大黄素对成纤维细胞增殖有抑制作用,其中40 μmol/L浓度组最明显;瘢痕组织及细胞测序结果提示,差异基因在细胞外基质与受体相互作用通路中显著富集,且组织与细胞拥有共同差异基因THBS1;过表达分析结果提示,差异基因THBS1在PI3K-Akt信号通路中显著富集。 结论 芦荟大黄素可能通过下调THBS1,抑制PI3K-Akt通路,从而降低术后腭部瘢痕组织来源的成纤维细胞增殖活性。
英文摘要
ObjectiveTo propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway.MethodsBy cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis.ResultsAloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway.ConclusionAloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
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