Impact of angiogenic activation and inhibition on miRNA profiles of human retinal endothelial cells
| Autor: | Tristan Reuer, Bjoern Gruening, Andreas Stahl, Franziska Ludwig, Johanna M. Walz, Clemens Lange, Lothar Faerber, Stefaniya Boneva, Guenther Schlunck, Hansjuergen Agostini, Bertan Cakir, Thomas Wecker, Pei pei Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis Recombinant Fusion Proteins Cellular differentiation Angiogenesis Inhibitors Biology Retina Transcriptome Cellular and Molecular Neuroscience chemistry.chemical_compound Cell surface receptor Ranibizumab microRNA Humans Retinopathy of Prematurity Kinase activity Endothelial Cells Cell Differentiation Sensory Systems Bevacizumab Intracellular signal transduction Vascular endothelial growth factor MicroRNAs Ophthalmology Receptors Vascular Endothelial Growth Factor chemistry Cancer research |
| Zdroj: | Experimental Eye Research. 181:98-104 |
| ISSN: | 0014-4835 |
| DOI: | 10.1016/j.exer.2019.01.006 |
| Popis: | Background Human retinal microvascular endothelial cells (HRMVECs) are involved in the pathogenesis of retinopathy of prematurity. In this study, the microRNA (miRNA) expression profiles of HRMVECs were investigated under resting conditions, angiogenic stimulation (VEGF treatment) and anti-VEGF treatment. Materials and methods The miRNA profiles of HRMVECs under resting and angiogenic conditions (VEGF treatment), as well as after addition of aflibercept, bevacizumab or ranibizumab were evaluated by analyzing the transcriptome of small non-coding RNAs. Differentially expressed miRNAs were validated using qPCR and classified using Gene Ontology enrichment analysis. Results Ten miRNAs were found to be significantly changed more than 2-fold. Seven of these miRNAs were changed between resting conditions and angiogenic stimulation. Four of these miRNAs (miR-139-5p/-3p and miR-335-5p/-3p) were validated by qPCR in independent experiments and were found to be associated with angiogenesis and cell migration in Gene Ontology analysis. In addition, analysis of the most abundant miRNAs in the HRMVEC miRNome (representing at least 1% of the miRNome) was conducted and identified miR-21-5p, miR-29a-3p, miR-100-5p and miR-126-5p/-3p to be differently expressed by at least 15% between resting conditions and angiogenic conditions. These miRNAs were found to be associated with apoptotic signaling, regulation of kinase activity, intracellular signal transduction, cell surface receptor signaling and positive regulation of cell differentiation in Gene Ontology analysis. No differentially regulated miRNAs between angiogenic stimulation and angiogenic stimulation plus anti-VEGF treatment were identified. Conclusion In this study we characterized the miRNA profile of HRMVECs under resting, angiogenic and anti-angiogenic conditions and identified several miRNAs of potential pathophysiologic importance for angioproliferative retinal diseases. Our results have implications for possible miRNA-targeted angiomodulatory approaches in diseases like diabetic retinopathy or retinopathy of prematurity. |
| Databáze: | OpenAIRE |
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