Identification of novel key molecular signatures in the pathogenesis of experimental diabetic retinopathy

被引:6
作者
Liu, Caiying [1 ,2 ,3 ]
Zhu, Tong [1 ,2 ,3 ]
Zhang, Jieping [1 ,2 ,3 ]
Wang, Juan [1 ,2 ,3 ]
Gao, Furong [1 ,2 ,3 ]
Ou, Qingjian [2 ,3 ]
Jin, Caixia [1 ,2 ,3 ]
Xu, Jing-Ying [1 ,2 ,3 ]
Zhang, Jingfa [4 ]
Tian, Haibin [1 ,2 ,3 ]
Xu, Guo-Tong [1 ,2 ,3 ,5 ]
Lu, Lixia [1 ,2 ,3 ]
机构
[1] Tongji Univ, Shanghai Tenth Peoples Hosp, Sch Med, Lab Clin Visual Sci Tongji Eye Inst,Dept Ophthalm, Shanghai, Peoples R China
[2] Tongji Univ, Sch Med, Dept Pharmacol, Shanghai, Peoples R China
[3] Tongji Univ, Sch Med, Dept Biochem & Mol Biol, Shanghai, Peoples R China
[4] Shanghai Jiao Tong Univ, Shanghai First Peoples Hosp, Dept Ophthalmol, Shanghai Gen Hosp, Shanghai, Peoples R China
[5] Tongji Univ, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
bioinformatics; diabetic retinopathy; fatty acid metabolism; OXIDATIVE STRESS; GENE-EXPRESSION; RECEPTOR; INSULIN; LENGSIN; INFLAMMATION; ANGIOGENESIS; METHYLATION; RESPONSES; PROTEINS;
D O I
10.1002/iub.2544
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Deep mining of the molecular mechanisms underlying diabetic retinopathy (DR) is critical for the development of novel therapeutic targets. This study aimed to identify key molecular signatures involved in experimental DR on the basis of integrated bioinformatics analysis. Four datasets consisting of 37 retinal samples were downloaded from the National Center of Biotechnology Information Gene Expression Omnibus. After batch-effect adjustment, bioinformatics tools such as Networkanalyst, Enrichr, STRING, and Metascape were used to evaluate the differentially expressed genes (DEGs), perform enrichment analysis, and construct protein-protein interaction networks. The hub genes were identified using Cytoscape software. The DEGs of interest from the meta-analysis were confirmed by quantitative reverse transcription-polymerase chain reaction in diabetic rats and a high-glucose-treated retinal cell model, respectively. A total of 743 DEGs related to lens differentiation, insulin resistance, and high-density lipoprotein (HDL) cholesterol metabolism were obtained using the meta-analysis. Alterations of dynamic gene expression in the chloride ion channel, retinol metabolism, and fatty acid metabolism were involved in the course of DR in rats. Importantly, H3K27m3 modifications regulated the expression of most DEGs at the early stage of DR. Using an integrated bioinformatics approach, novel molecular signatures were obtained for different stages of DR progression, and the findings may represent distinct therapeutic strategies for DR patients.
引用
收藏
页码:1307 / 1324
页数:18
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