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The molecular mechanism responsible for HbSC retinopathy may depend on the action of the angiogenesis-related genes ROBO1 and SLC38A5.
da Silva Costa, Sueli Matilde; Ito, Mirta Tomie; da Cruz, Pedro Rodrigues Sousa; De Souza, Bruno Batista; Rios, Vinicius Mandolesi; Bertozzo, Victor de Haidar E; Camargo, Ana Carolina Lima; Viturino, Marina Gonçalves Monteiro; Lanaro, Carolina; de Albuquerque, Dulcinéia Martins; do Canto, Amanda Morato; Saad, Sara Teresinha Olalla; Ospina-Prieto, Stephanie; Ozelo, Margareth Castro; Costa, Fernando Ferreira; de Melo, Mônica Barbosa.
Afiliação
  • da Silva Costa SM; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • Ito MT; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • da Cruz PRS; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • De Souza BB; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • Rios VM; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • Bertozzo VHE; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • Camargo ACL; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • Viturino MGM; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
  • Lanaro C; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • de Albuquerque DM; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • do Canto AM; Departamento de Medicina Translacional, Faculdade de Ciências Médicas, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • Saad STO; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • Ospina-Prieto S; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • Ozelo MC; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • Costa FF; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
  • de Melo MB; Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
Exp Biol Med (Maywood) ; 249: 10070, 2024.
Article em En | MEDLINE | ID: mdl-39114443
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Imunológicos / Neovascularização Retiniana / Proteínas Roundabout / Proteínas do Tecido Nervoso Limite: Adult / Female / Humans / Male Idioma: En Revista: Exp Biol Med (Maywood) Assunto da revista: BIOLOGIA / FISIOLOGIA / MEDICINA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Imunológicos / Neovascularização Retiniana / Proteínas Roundabout / Proteínas do Tecido Nervoso Limite: Adult / Female / Humans / Male Idioma: En Revista: Exp Biol Med (Maywood) Assunto da revista: BIOLOGIA / FISIOLOGIA / MEDICINA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça