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Interplay of endothelial-mesenchymal transition, inflammation, and autophagy in proliferative diabetic retinopathy pathogenesis

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机构: [1]Department of Ophthalmology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China. [2]Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, China. [3]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guang-dong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
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关键词: Proliferative diabetic retinopathy Transcriptome sequencing Endothelial-mesenchymal transition Inflammation Autophagy

摘要:
Assessment and validation of endothelial-mesenchymal transition (EndoMT) in the retinal endothelium of patients with proliferative diabetic retinopathy (PDR) at the level of retinal and vitreous specimens, and preliminary discussion of its regulatory mechanisms.Transcriptome sequencing profiles of CD31+ cells from 9 retinal fibrovascular mem-branes (FVMs) and 4 postmortem retinas were downloaded from GEO databases to analyze EndoMT-related differentially expressed genes (DEGs). Then, 42 PDR patients and 34 idiopathic macular holes (IMH) patients were enrolled as the PDR and control groups, respectively. Vitreous humor (VH) samples were collected, and the expression of EndoMT-related proteins was quantified by enzyme-linked immunosorbent assay.A total of 5845 DEGs were identified, and we subsequently focused on the analysis of 24 EndoMT-related marker genes, including the trigger of EndoMT, endothelial genes, mesenchymal genes, transcription factors, inflammatory factors, and autophagy markers. Six of these genes were selected for protein assay validation in VH, showing increased mesenchymal marker (type I collagen α 2 chain, COL1A2) and decreased endothelial marker (VE-cadherin, CDH5) accompanied by increased TGFβ, IL-1β, LC3B and P62 in PDR patients. In addition, anti-VEGF therapy could enhance EndoMT-related phenotypes.EndoMT may underlie the pathogenesis of PDR, and the induction and regulation correlate with autophagy defects and the inflammatory response.© 2024 The Authors.

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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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大类 | 4 区 综合性期刊
小类 | 4 区 综合性期刊
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Q2 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Ophthalmology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
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