小梁网中地塞米松诱导的潜在基因变化的表达谱分析。

Expression profile analysis to identify potential gene changes induced by dexamethasone in the trabecular meshwork.

作者信息

Wei Miao, Chen Lu-Ming, Huang Ze-Yu, Zhang Guo-Wei, Guan Huai-Jin, Ji Min

机构信息

Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.

Dalian Medical University, Dalian 116000, Liaoning Province, China.

出版信息

Int J Ophthalmol. 2022 Aug 18;15(8):1240-1248. doi: 10.18240/ijo.2022.08.03. eCollection 2022.

DOI:10.18240/ijo.2022.08.03

PMID:36017046

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9358186/

Abstract

AIM

To investigate potential gene changes in trabecular meshwork (TM) induced by dexamethasone (DEX) in steroid-induced glaucoma (SIG).

METHODS

The expression data of 24 cases from a public functional genomics data were sorted to identify the mechanisms of action of DEX on the TM. The relationships of the differentially expressed genes (DEGs) were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the hub genes were screened by the Search Tool for the Retrieval of Interacting Genes Database (STRING) and Cytoscape tools. Finally, human TM cells (HTMCs) were treated with DEX to preliminarily explore the function of hub genes.

RESULTS

Totally 47 DEGs, including 21 downregulated and 26 upregulated genes were identified. The primary enriched results of the DEGs consisted of inflammatory response, extracellular matrix (ECM), negative regulation of cell proliferation, TNF signalling pathway and the regulation of tryptophan channels by inflammatory mediators. Subsequently, pro-melanin-enriched hormone (PMCH) and Bradykinin B1 receptor (BDKRB1) were screened as hub genes. It is verified in GSE37474 data set. Western blot and quantitative real-time polymerase chain reaction (qPCR) results showed that protein and RNA expression levels of BDKRB1 were significantly decreased after DEX treatment, while PMCH was not significantly changed.

CONCLUSION

BDKRB1 may be a key gene involved in SIG onset, providing a suitable therapeutic target for improving the prognosis of SIG patients.

摘要

目的

研究地塞米松（DEX）诱导的激素性青光眼（SIG）小梁网（TM）中的潜在基因变化。

方法

对来自公共功能基因组学数据的24例样本的表达数据进行分类，以确定DEX对TM的作用机制。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析对差异表达基因（DEG）的关系进行富集。此外，通过检索相互作用基因数据库（STRING）和Cytoscape工具筛选枢纽基因。最后，用地塞米松处理人TM细胞（HTMC）以初步探索枢纽基因的功能。

结果

共鉴定出47个DEG，包括21个下调基因和26个上调基因。DEG的主要富集结果包括炎症反应、细胞外基质（ECM）、细胞增殖的负调控、TNF信号通路以及炎症介质对色氨酸通道的调控。随后，筛选出促黑素富集激素（PMCH）和缓激肽B1受体（BDKRB1）作为枢纽基因。在GSE37474数据集中得到验证。蛋白质印迹和定量实时聚合酶链反应（qPCR）结果显示，DEX处理后BDKRB1的蛋白质和RNA表达水平显著降低，而PMCH无显著变化。