S. M. da Silva Costa, M. T. Ito, Pedro Rodrigues Sousa da Cruz, B. B. de Souza, V. M. Rios, V. D. H. E. Bertozzo, Ana Carolina Lima Camargo, M. Viturino, C. Lanaro, D. M. de Albuquerque, Amanda M. do Canto, Sara Teresinha Olalla Saad, Stephanie Ospina-Prieto, M. Ozelo, F. F. Costa, M. B. de Melo
{"title":"The molecular mechanism responsible for HbSC retinopathy may depend on the action of the angiogenesis-related genes ROBO1 and SLC38A5","authors":"S. M. da Silva Costa, M. T. Ito, Pedro Rodrigues Sousa da Cruz, B. B. de Souza, V. M. Rios, V. D. H. E. Bertozzo, Ana Carolina Lima Camargo, M. Viturino, C. Lanaro, D. M. de Albuquerque, Amanda M. do Canto, Sara Teresinha Olalla Saad, Stephanie Ospina-Prieto, M. Ozelo, F. F. Costa, M. B. de Melo","doi":"10.3389/ebm.2024.10070","DOIUrl":null,"url":null,"abstract":"HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1, an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/ebm.2024.10070","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1, an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis.
期刊介绍:
Experimental Biology and Medicine (EBM) is a global, peer-reviewed journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. EBM provides both research and review articles as well as meeting symposia and brief communications. Articles in EBM represent cutting edge research at the overlapping junctions of the biological, physical and engineering sciences that impact upon the health and welfare of the world''s population.
Topics covered in EBM include: Anatomy/Pathology; Biochemistry and Molecular Biology; Bioimaging; Biomedical Engineering; Bionanoscience; Cell and Developmental Biology; Endocrinology and Nutrition; Environmental Health/Biomarkers/Precision Medicine; Genomics, Proteomics, and Bioinformatics; Immunology/Microbiology/Virology; Mechanisms of Aging; Neuroscience; Pharmacology and Toxicology; Physiology; Stem Cell Biology; Structural Biology; Systems Biology and Microphysiological Systems; and Translational Research.