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针对血管钙化的姜黄素靶向分析与鉴定。

Target analysis and identification of curcumin against vascular calcification.

机构信息

Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China.

School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China.

出版信息

Sci Rep. 2024 Jul 28;14(1):17344. doi: 10.1038/s41598-024-67776-2.

Abstract

To investigate the mechanism of curcumin (CUR) on vascular calcification (VC), we screen for common targets of CUR and atherosclerosis and verify the targets genes in vivo and in vitro experiments. The common targets of CUR and AS were screened and obtained using different databases. These target genes were analyzed by GO and KEGG pathway enrichment analysis. PPI network analysis was performed and to analyze the key targets. A rat VC model was constructed and CUR was fed for three weeks. The changes of vascular structure and calcium salt deposition were observed in H&E and Von Kossa staining. Further, the expression of these target proteins was detected in the primary VSMCs of VC. The 31 common targets were obtained. GO functional enrichment analysis obtained 1284 terms and KEGG pathway enriched 66 pathways. The key genes were identified in the cytoHubba plugin. The molecular docking analysis showed that CUR bound strongly to EGFR, STAT3 and BCL2. The animal experiments showed the deposition calcium salt reduced by the CUR administration. These proteins BMP2, RUNX2, EGFR, STAT3 and BAX expression were upregulated in VC group and CUR attenuated the upregulated expression. The signal protein Akt and p65 expression increased in VC group and decreased in CUR group. We identified some common target genes of CUR and AS and identified these key genes. The anti-VC effect of CUR was associated with the inhibition of upregulation of EGFR, STAT3 and RUNX2 expression in VSMCs.

摘要

为了研究姜黄素(CUR)对血管钙化(VC)的作用机制,我们筛选了 CUR 和动脉粥样硬化的共同靶点,并在体内和体外实验中验证了这些靶点基因。使用不同的数据库筛选和获得了 CUR 和 AS 的共同靶点。通过 GO 和 KEGG 通路富集分析对这些靶基因进行了分析。进行了 PPI 网络分析,以分析关键靶点。构建大鼠 VC 模型并喂养 CUR 三周。通过 H&E 和 Von Kossa 染色观察血管结构和钙盐沉积的变化。进一步在 VC 的原代 VSMCs 中检测这些靶蛋白的表达。获得了 31 个共同靶点。GO 功能富集分析获得了 1284 个术语,KEGG 通路富集了 66 条通路。在 cytoHubba 插件中确定了关键基因。分子对接分析表明 CUR 与 EGFR、STAT3 和 BCL2 结合紧密。动物实验表明 CUR 给药后钙盐沉积减少。这些蛋白 BMP2、RUNX2、EGFR、STAT3 和 BAX 在 VC 组中的表达上调,而 CUR 则减弱了这种上调表达。信号蛋白 Akt 和 p65 在 VC 组中表达增加,在 CUR 组中表达减少。我们鉴定了 CUR 和 AS 的一些共同靶点,并确定了这些关键基因。CUR 的抗 VC 作用与抑制 VSMCs 中 EGFR、STAT3 和 RUNX2 表达的上调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5798/11284211/40e69603b0d3/41598_2024_67776_Fig1_HTML.jpg

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