Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy

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Bertozzo, Victor de Haidar E. ; Costa, Sueli Matilde da Silva ; Ito, Mirta Tomie ; da Cruz, Pedro Rodrigues Sousa ; Souza, Bruno Batista ; Rios, Vinicius Mandolesi ; Viturino, Marina Goncalves Monteiro ; de Castro, Julia Nicoliello Pereira ; Rodrigues, Thiago Adalton Rosa ; Lanaro, Carolina ; de Albuquerque, Dulcineia Martins ; Saez, Roberta Casagrande ; Saad, Sara Teresinha Olalla ; Ozelo, Margareth Castro ; Costa, Fernando Ferreira ; de Melo, Monica Barbosa

• Document type: Journal article
• Source: Experimental Biology and Medicine; v. 248, n. 8, p. 8-pg., 2023-04-03.

Abstract

Among sickle cell anemia (SCA) complications, proliferative sickle cell retinopathy (PSCR) is one of the most important, being responsible for visual impairment in 10-20% of affected eyes. The aim of this study was to identify differentially expressed genes (DEGs) present in pathways that may be implicated in the pathophysiology of PSCR from the transcriptome profile analysis of endothelial progenitor cells. RNA-Seq was used to compare gene expression profile of circulating endothelial colony-forming cells (ECFCs) from HbSS patients with and without PSCR. Furthermore, functional enrichment analysis and protein-protein interaction (PPI) networks were performed to gain further insights into biological functions. The differential expression analysis identified 501 DEGs, when comparing the groups with and without PSCR. Furthermore, functional enrichment analysis showed associations of the DEGs in 200 biological processes. Among these, regulation of mitogen-activated protein (MAP) kinase activity, positive regulation of phosphatidylinositol 3-kinase (PI3K), and positive regulation of Signal Transducer and Activator of Transcription (STAT) receptor signaling pathway were observed. These pathways are associated with angiogenesis, cell migration, adhesion, differentiation, and proliferation, important processes involved in PSCR pathophysiology. Moreover, our results showed an over-expression of VEGFC (vascular endothelial growth factor-C) and FLT1 (Fms-Related Receptor Tyrosine Kinase 1) genes, when comparing HbSS patients with and without PSCR. These results may indicate a possible association between VEGFC and FLT1 receptor, which may activate signaling pathways such as PI3K/AKT and MAPK/ERK and contribute to the mechanisms implicated in neovascularization. Thus, our findings contain preliminary results that may guide future studies in the field, since the molecular mechanisms of PSCR are still poorly understood. (AU)

• FAPESP's process: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/14255-6 - RNA-seq technique application in endothelial and leukocyte cells transcription profile evaluation in sickle cell retinopathy
• Grantee: Sueli Matilde da Silva Costa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants