Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery

Abstract Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibr...

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Autores principales:	Cynthia Yu-Wai-Man, Nicholas Owen, Jonathan Lees, Aristides D. Tagalakis, Stephen L. Hart, Andrew R. Webster, Christine A. Orengo, Peng T. Khaw
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c0371687dca468ab80f8f19c7cf2ac1
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spelling	oai:doaj.org-article:5c0371687dca468ab80f8f19c7cf2ac12021-12-02T11:52:40ZGenome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery10.1038/s41598-017-05780-52045-2322https://doaj.org/article/5c0371687dca468ab80f8f19c7cf2ac12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05780-5https://doaj.org/toc/2045-2322Abstract Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues.Cynthia Yu-Wai-ManNicholas OwenJonathan LeesAristides D. TagalakisStephen L. HartAndrew R. WebsterChristine A. OrengoPeng T. KhawNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cynthia Yu-Wai-Man Nicholas Owen Jonathan Lees Aristides D. Tagalakis Stephen L. Hart Andrew R. Webster Christine A. Orengo Peng T. Khaw Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
description	Abstract Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues.
format	article
author	Cynthia Yu-Wai-Man Nicholas Owen Jonathan Lees Aristides D. Tagalakis Stephen L. Hart Andrew R. Webster Christine A. Orengo Peng T. Khaw
author_facet	Cynthia Yu-Wai-Man Nicholas Owen Jonathan Lees Aristides D. Tagalakis Stephen L. Hart Andrew R. Webster Christine A. Orengo Peng T. Khaw
author_sort	Cynthia Yu-Wai-Man
title	Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
title_short	Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
title_full	Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
title_fullStr	Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
title_full_unstemmed	Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
title_sort	genome-wide rna-sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5c0371687dca468ab80f8f19c7cf2ac1
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Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery

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