1. A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium
- Author
-
Emri, E, Kortvely, E, Dammeier, S, Klose, F, Simpson, D, Hollander, AI, Ueffing, M, Lengyel, I, Acar, E, Ajana, S, Arango?gonzalez, B, Armento, A, Badura, F, Bartz?schmidt, U, Biarnes, M, Borrell, A, de Breuk, A, De la Cerda, B, Colijn, Annemarie, Cougnard?gregoire, A, Delcourt, C, Diether, S, Endermann, T, Ferraro, LL, Garcia, M, Heesterbeek, TJ, Honisch, S, Kilger, E, Klaver, Caroline, Langen, H, Meester - Smoor, Magda, Merle, BMJ, Mones, J, Nogoceke, E, Peto, T, Pool, FM, Rodriguez, E, Sousa, J, Thee, Eric, Verzijden, T (Timo), Zumbansen, M, and Ophthalmology
- Subjects
0301 basic medicine ,proteome ,retinal pigment epithelium ,lcsh:TX341-641 ,Biology ,medicine.disease_cause ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Article ,Transforming Growth Factor beta1 ,Transcriptome ,Macular Degeneration ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,TGFB1 ,Cell Adhesion ,Electric Impedance ,medicine ,Humans ,Micronutrients ,Cell adhesion ,age-related macular degeneration ,Cells, Cultured ,Nutrition and Dietetics ,Retinal pigment epithelium ,Microvilli ,Pigmentation ,zinc ,Cell Polarity ,gene set enrichment ,Extracellular Matrix ,Cell biology ,Oxidative Stress ,Protein Transport ,secretome ,030104 developmental biology ,medicine.anatomical_structure ,Secretory protein ,Cell culture ,Proteome ,030221 ophthalmology & optometry ,sense organs ,transcriptome ,lcsh:Nutrition. Foods and food supply ,Oxidative stress ,Signal Transduction ,Food Science ,Extracellular matrix organization - Abstract
In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ±, 79.3%, basal supplementation: 424.9 ±, 116.8%, compared to control: 317.5 ±, 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1.
- Published
- 2020
- Full Text
- View/download PDF