Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina

Abstract Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks wit...

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Autores principales:	A. M. Olivares, A. S. Jelcick, J. Reinecke, B. Leehy, A. Haider, M. A. Morrison, L. Cheng, D. F. Chen, M. M. DeAngelis, N. B. Haider
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05f23ea97c784d9dafad3e28f558713e
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spelling	oai:doaj.org-article:05f23ea97c784d9dafad3e28f558713e2021-12-02T15:05:22ZMultimodal Regulation Orchestrates Normal and Complex Disease States in the Retina10.1038/s41598-017-00788-32045-2322https://doaj.org/article/05f23ea97c784d9dafad3e28f558713e2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00788-3https://doaj.org/toc/2045-2322Abstract Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.A. M. OlivaresA. S. JelcickJ. ReineckeB. LeehyA. HaiderM. A. MorrisonL. ChengD. F. ChenM. M. DeAngelisN. B. HaiderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. M. Olivares A. S. Jelcick J. Reinecke B. Leehy A. Haider M. A. Morrison L. Cheng D. F. Chen M. M. DeAngelis N. B. Haider Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
description	Abstract Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.
format	article
author	A. M. Olivares A. S. Jelcick J. Reinecke B. Leehy A. Haider M. A. Morrison L. Cheng D. F. Chen M. M. DeAngelis N. B. Haider
author_facet	A. M. Olivares A. S. Jelcick J. Reinecke B. Leehy A. Haider M. A. Morrison L. Cheng D. F. Chen M. M. DeAngelis N. B. Haider
author_sort	A. M. Olivares
title	Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
title_short	Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
title_full	Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
title_fullStr	Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
title_full_unstemmed	Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
title_sort	multimodal regulation orchestrates normal and complex disease states in the retina
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/05f23ea97c784d9dafad3e28f558713e
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Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina

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