Impact of angiogenic activation and inhibition on miRNA profiles of human retinal endothelial cells. (April 2019)

• Record Type: Journal Article
• Authors: Walz, Johanna M.; Wecker, Thomas; Zhang, Pei Pei; Cakir, Bertan; Gruening, Bjoern; Agostini, Hansjuergen; Reuer, Tristan; Ludwig, Franziska; Boneva, Stefaniya; Faerber, Lothar; Lange, Clemens; Schlunck, Guenther R.; Stahl, Andreas
• Is Part Of: Experimental eye research. Volume 181(2019)
• Page Start: 98
• Page End: 104
• Publication Date: 2019-04
• Subjects: microRNA -- Retinal endothelial cells -- Angiogenesis -- Vascular endothelial growth factor -- Next generation sequencing -- Gene ontology enrichment analysis; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2019.01.006
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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. Highlights: First characterization of HRMVECs miRNA profile. Analysing the impact of anti-VEGF treatment on HRMVEC miRNA expression. Identifying novel and important miRNAs for angioproliferative retinal diseases. Describing potential miRNA targets for angiomodulatory treatments.