ABSTRACT

Background

Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris.

Methods

TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis.

Results

The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs.

Conclusions

The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling.

中文翻译：

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RNA-Seq分析组织驻留巨噬细胞在胆脂瘤进展中的炎症和稳态作用

摘要

背景

组织驻留巨噬细胞 (TRMØs) 可以作为先天免疫哨兵，保护身体免受微生物入侵和刺激物质（如胆脂瘤中的胆固醇晶体）的侵害，并通过清洁不需要的细胞碎片来保持组织完整性。

方法

从胆脂瘤患者作为实验组和无胆脂瘤患者作为对照组获得切开的中耳组织中的TRMØ。通过分析炎症、组织修复和体内平衡的 GO 过程、KEGG 和 GSEA 通路，在两组之间进行了 TRMØ 的差异基因表达谱分析。

结果

目前的研究表明，与没有胆脂瘤的患者相比，7060 个基因中有 145 个显着上调（logFC>2 和 FDR <0.05）。对过表达基因的 GO 过程、GSEA 和 Cytoscape 分析表明，TRMØ 增强的炎症和抗感染功能存在中性粒细胞功能、白细胞迁移和涉及受体和信号通路的适应性免疫反应。而 TRMØs 的稳态和修复功能受到上调基因的影响，例如过度表达的 keratin-13 有助于形成外部角化鳞状上皮层，以及过度表达的 MMPs 激活细胞外基质分子以促进炎症和干扰组织重塑。此外，74 个下调基因（logFC<-2 和 FDR <0.

结论

胆脂瘤中的细胞和分子水平可归因于慢性感染和涉及细胞完整性和组织重塑的几个受干扰的细胞生物学过程。