Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.
Victor de Haidar E BertozzoSueli Matilde da Silva CostaMirta Tomie ItoPedro Rodrigues Sousa da CruzBruno Batista SouzaVinicius Mandolesi RiosMarina Gonçalves Monteiro ViturinoJúlia Nicoliello Pereira de CastroThiago Adalton Rosa RodriguesCarolina LanaroDulcinéia Martins de AlbuquerqueRoberta Casagrande SaezSara Teresinha Olalla SaadMargareth Castro OzeloFernando Ferreira CostaMônica Barbosa de MeloPublished in: Experimental biology and medicine (Maywood, N.J.) (2023)
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.
Keyphrases
- tyrosine kinase
- signaling pathway
- pi k akt
- vascular endothelial growth factor
- induced apoptosis
- cell cycle arrest
- rna seq
- endothelial cells
- epidermal growth factor receptor
- protein protein
- cell migration
- genome wide
- single cell
- genome wide identification
- epithelial mesenchymal transition
- cell proliferation
- small molecule
- risk factors
- poor prognosis
- acute myeloid leukemia
- protein kinase
- copy number
- dna methylation
- optical coherence tomography
- endoplasmic reticulum stress
- cell death
- transcription factor
- chronic kidney disease
- immune response
- genome wide analysis
- binding protein
- long non coding rna
- biofilm formation
- nuclear factor