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糖尿病性黄斑水肿神经血管耦合相关生物标志物的鉴定及机制分析

Identification and mechanistic analysis of neurovascular coupling related biomarkers for diabetic macular edema.

作者信息

Chen Tianpeng, Sheng Shufan, Chen Jing, Wang Xiaole, Shang Yanxing, Duan Chengwei, Liang Caixia, Song Yu, Zhang Dongmei

机构信息

Medical Research Center, Affiliated Hospital 2 of Nantong University, Nantong, China.

Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit, Medical Research Center, Nantong First People's Hospital, Nantong, China.

出版信息

Front Mol Biosci. 2024 Sep 13;11:1332842. doi: 10.3389/fmolb.2024.1332842. eCollection 2024.

DOI:10.3389/fmolb.2024.1332842
PMID:39347501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11427358/
Abstract

INTRODUCTION

Diabetic macular edema (DME) is a major cause of vision loss in the sick with diabetic retinopathy. The occurrence of DME is closely related to the breakdown of neurovascular coupling; however, its underlying mechanism has not been fully elucidated. The aim of this study was to investigate the diagnostic biomarkers and potential molecular mechanisms associated with neurovascular coupling in DME.

METHODS

The differential expression analysis, STEM, and WGCNA were performed from GSE160306 to identify hub genes. The gene expression was validated by RT-qPCR. The relevant mechanisms of action were investigated through GO, KEGG, and GSEA analyses, as well as co-expression networks. Additionally, the LASSO regression analysis and a nomogram were used to demonstrate the diagnostic effectiveness of the model. Finally, the GenDoma platform was utilized to identify drugs with potential therapeutic effects on DME.

RESULTS

Neurotrophic factor receptor (NGFR) was identified as a hub gene related to neurovascular coupling and DME. The expression of NGFR was verified by RT-qPCR in cells. GSEA analysis indicated that high expression of NGFR may affect immunity and inflammatory pathway, thereby regulating neurovascular coupling and mediating the development of DME. The NGFR co-expression network was constructed, which exhibited the correlation with the neurotrophin signaling pathway. Moreover, a diagnostic model for DME based on NGFR and PREX1 demonstrated relatively good diagnostic performance using LASSO regression analysis and the nomogram. And then the GenDoma platform identified drugs with potential therapeutic effects on DME.

CONCLUSION

The high expression of NGFR may lead to abnormal neurovascular coupling and participate in the occurrence of DME by regulating the immunity, inflammatory and neurotrophin signaling pathway. Detection of NGFR and related expression genes may be beneficial for monitoring the occurrence and development of DME.

摘要

引言

糖尿病性黄斑水肿(DME)是糖尿病视网膜病变患者视力丧失的主要原因。DME的发生与神经血管耦合功能障碍密切相关;然而,其潜在机制尚未完全阐明。本研究旨在探讨与DME中神经血管耦合相关的诊断生物标志物和潜在分子机制。

方法

从GSE160306数据集进行差异表达分析、STEM分析和加权基因共表达网络分析(WGCNA)以识别枢纽基因。通过逆转录定量聚合酶链反应(RT-qPCR)验证基因表达。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)以及共表达网络研究相关作用机制。此外,采用套索回归分析和列线图来证明该模型的诊断效能。最后,利用GenDoma平台识别对DME具有潜在治疗作用的药物。

结果

神经营养因子受体(NGFR)被鉴定为与神经血管耦合和DME相关的枢纽基因。通过RT-qPCR在细胞中验证了NGFR的表达。GSEA分析表明,NGFR的高表达可能影响免疫和炎症途径,从而调节神经血管耦合并介导DME的发展。构建了NGFR共表达网络,其与神经营养因子信号通路存在相关性。此外,基于NGFR和PREX1的DME诊断模型经套索回归分析和列线图显示出相对良好的诊断性能。然后,GenDoma平台识别出对DME具有潜在治疗作用的药物。

结论

NGFR的高表达可能导致神经血管耦合异常,并通过调节免疫、炎症和神经营养因子信号通路参与DME的发生。检测NGFR及相关表达基因可能有助于监测DME的发生和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c49/11427358/1061cb8b7fb1/fmolb-11-1332842-g008.jpg
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