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体外研究和基因芯片的综合分析揭示了海藻糖对翼状胬肉发病机制的新型抑制作用。

Integrative analysis of ex vivo studies and microarray reveals the novel inhibitor effects of trehalose on the pathogenesis of pterygium.

机构信息

Department of Ophthalmology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.

Department of Cancer Molecular Biology, Institution of Health Sciences, Pamukkale University, Denizli, Turkey.

出版信息

Chem Biol Drug Des. 2024 Jul;104(1):e14571. doi: 10.1111/cbdd.14571.

Abstract

Pterygium is a frequent eye surface condition that is characterized by a high rate of proliferation, fibrovascular development, cellular migration, corneal infiltration, and angiogenesis. We investigated that ex vivo primary pterygium and conjunctival cell cultures were generated to analyze the effect of trehalose on cellular proliferation. After trehalose treatment, we performed microarray analysis to evaluate changes in the mRNA profile. We analyzed gene ontology (GO) and KEGG pathways to identify hub genes that changed expression levels after treatment and were associated with pterygium development. We selected three genes to verify their expression levels using qRT-PCR. The study also evaluated the impact of trehalose treatment on cell migration through a wound-healing assay. Our results suggested that pterygium cell proliferation was inhibited in a dose-dependent manner by trehalose. 2354 DEG were identified in pterygium and conjunctiva cells treated with trehalose compared to untreated groups. Functional enrichment analysis showed that differentially expressed mRNAs are involved in proliferation, vasculature development, and cell migration. We identified ten hub genes including upregulated (RANBP3L, SLC5A3, RERG, ANKRD1, DHCR7, RAB27B, GPRC5B, MSMO1, ASPN, DRAM1) and downregulated (TNC, PTGS2, GREM2, NPTX1, NR4A1, HMOX1, CXCL12, IL6, MYH2, TXNIP). Microarray analysis and functional investigations suggest that trehalose affects the pathogenesis of pterygium by modifying the expression of genes involved in crucial pathways related to cell function.

摘要

翼状胬肉是一种常见的眼表面疾病,其特征是增殖率高、纤维血管发育、细胞迁移、角膜浸润和血管生成。我们研究了体外原发性翼状胬肉和结膜细胞培养物,以分析海藻糖对细胞增殖的影响。在海藻糖处理后,我们进行了微阵列分析,以评估 mRNA 谱的变化。我们分析了基因本体论(GO)和 KEGG 途径,以确定治疗后表达水平改变且与翼状胬肉发展相关的枢纽基因。我们选择了三个基因使用 qRT-PCR 验证它们的表达水平。该研究还通过划痕愈合试验评估了海藻糖处理对细胞迁移的影响。我们的结果表明,海藻糖以剂量依赖的方式抑制翼状胬肉细胞的增殖。与未处理组相比,用海藻糖处理的翼状胬肉和结膜细胞中鉴定出 2354 个差异表达基因。功能富集分析表明,差异表达的 mRNAs 参与增殖、血管发育和细胞迁移。我们确定了十个枢纽基因,包括上调(RANBP3L、SLC5A3、RERG、ANKRD1、DHCR7、RAB27B、GPRC5B、MSMO1、ASPN、DRAM1)和下调(TNC、PTGS2、GREM2、NPTX1、NR4A1、HMOX1、CXCL12、IL6、MYH2、TXNIP)。微阵列分析和功能研究表明,海藻糖通过修饰与细胞功能相关的关键途径中涉及的基因表达来影响翼状胬肉的发病机制。

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