从头皮银屑病中鉴定潜在的生物标志物和浸润免疫细胞。

Identification of potential biomarkers and infiltrating immune cells from scalp psoriasis.

机构信息

Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, China.

Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, China; Department of Dermatology, Guangdong Medical University, Zhanjiang, Guangdong, China.

出版信息

Gene. 2024 Jan 30;893:147918. doi: 10.1016/j.gene.2023.147918. Epub 2023 Oct 21.

DOI:10.1016/j.gene.2023.147918

PMID:37871808

Abstract

BACKGROUND

Scalp psoriasis seriously affects the appearance and psychological status of patients. The aim of this study was to investigate the effect and potential mechanism of RPL9 and TIFA in scalp psoriasis, so as to provide a precise and effective way for the clinical treatment of scalp psoriasis.

METHODS

The Gene Expression Omnibus (GEO) database was employed to download the GSE75343 dataset to search for differentially expressed genes (DEGs) in scalp psoriasis through Sangerbox. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) enrichment analysis, functional enrichment analysis, immune cell infiltration analysis, immune responses and correlation analysis with 12 hub genes were performed. Then, STRING was used to develop a protein-protein interaction (PPI) network, used Cytoscape to locate hub genes, and SVM-RFE and random forest were utilized to identified RPL9 as the targeted gene. TIFA-RPL9 interaction predictions were made viathe Open Targets Platform and Uniprot. Further, the RPL9 and TIFA expression, molecular mechanism, and function were assessed in scalp psoriasis.

RESULTS

Immunohistochemistry, qPCR, and western blotting verified that RPL9 and TIFA were highly expressed in lesional tissues of scalp psoriasis and IL17A-stimulated HaCaT cells. RPL9 knockdown effectively suppressed the proliferative capacity of IL17A-stimulated HaCaT cells in the CCK8 assay. The co-immunoprecipitation results revealed that RPL9 could interact with TIFA in IL17A-stimulated HaCaT cells. In qPCR and western blotting, RPL9 knockdown significantly inhibited TIFA at the mRNA and protein levels in IL17A-stimulated HaCaT cells. In ELISA, the secretion of TNF-α was markedly inhibited after downregulating RPL9 in IL17A-stimulated HaCaT cells.

CONCLUSION

To our knowledge, we have elucidated the expression and role of RPL9 and TIFA in scalp psoriatic skin and keratinocytes, and our findings confirm that RPL9 might act as a candidate therapeutic target for scalp psoriasis.

摘要

背景

头皮银屑病严重影响患者的外观和心理状态。本研究旨在探讨 RPL9 和 TIFA 在头皮银屑病中的作用及潜在机制，为头皮银屑病的临床治疗提供精准有效的方法。

方法

利用基因表达综合数据库（GEO）下载 GSE75343 数据集，通过 Sangerbox 搜索头皮银屑病中的差异表达基因（DEGs）。进行基因集富集分析（GSEA）和基因集变异分析（GSVA）富集分析、功能富集分析、免疫细胞浸润分析、免疫反应以及与 12 个枢纽基因的相关性分析。然后，利用 STRING 构建蛋白质-蛋白质相互作用（PPI）网络，使用 Cytoscape 定位枢纽基因，采用 SVM-RFE 和随机森林筛选 RPL9 作为靶向基因。利用 Open Targets Platform 和 Uniprot 预测 TIFA-RPL9 相互作用。进一步评估 RPL9 和 TIFA 在头皮银屑病中的表达、分子机制和功能。

结果

免疫组织化学、qPCR 和 Western blot 验证 RPL9 和 TIFA 在头皮银屑病皮损组织和 IL17A 刺激的 HaCaT 细胞中高表达。CCK8 实验证实 RPL9 敲低可有效抑制 IL17A 刺激的 HaCaT 细胞的增殖能力。共免疫沉淀结果显示，RPL9 可与 IL17A 刺激的 HaCaT 细胞中的 TIFA 相互作用。qPCR 和 Western blot 结果显示，RPL9 敲低可显著抑制 IL17A 刺激的 HaCaT 细胞中 TIFA 的 mRNA 和蛋白水平。ELISA 结果显示，下调 IL17A 刺激的 HaCaT 细胞中的 RPL9 可显著抑制 TNF-α的分泌。