Khong, JJ and Wang, LY and Smyth, GK and McNab, AA and Hardy, TG and Selva, D and Llamas, B and Jung, C-H and Sharma, S and Burdon, KP and Ebeling, PR and Craig, JE, Differential gene expression profiling of orbital adipose tissue in thyroid orbitopathy, Investigative Ophthalmology and Visual Science, 56, (11) pp. 6438-6447. ISSN 0146-0404 (2015) [Refereed Article]
Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
Purpose: We aimed to determine differentially expressed genes relevant to orbital inflammation and orbital fat expansion in thyroid orbitopathy (TO) using microarray gene profiling in a case-control study.
Methods: Human orbital adipose samples were obtained from individuals with active TO (n = 12), inactive TO (n = 21), and normal controls (n = 21). Gene expression profiles were examined using microarray analysis and were compared between active and inactive TO, and between active TO and normal controls. Top ranked differentially expressed genes were validated by real-time RT-PCR in an additional eight active TO, 13 inactive TO, and 11 normal controls and correlated with gene set enrichment analysis (GSEA) and molecular pathways analysis.
Results: Seven hundred twenty-one probes (683 genes) and 806 probes (735 genes) were significantly differentially expressed in comparing active to inactive TO and in comparing active TO to healthy controls, respectively. All selected genes were confirmed to be differentially expressed by real-time RT-PCR. Multiple top ranked genes in active versus inactive TO comparison are overrepresented by immune and inflammatory response genes. They include defensins (DEFA1, DEFA1B, DEFA3), which were overexpressed by 3.05- to 4.14-fold and TIMD4 by 4.20-fold. Markers for adipogenesis were overexpressed including SCD, FADS1, and SCDP1. Gene set enrichment analysis revealed dysregulation of epigenetic signatures, T-cell activation, Th1 differentiation, defensin pathway, cell adhesion, cytoskeleton organization, apoptosis, cell cycling, and lipid metabolism in active TO.
Conclusions: Active TO is characterized by upregulation of genes involved in cell-mediated immune, innate immune, and inflammatory response and enhanced orbital adipogenesis. TIMD4, DEFA1, DEFA1B, and DEFA3 genes may be involved in the innate immune-mediated orbital inflammation in TO. Epigenetic mechanisms may play a role in the pathogenesis of TO.
|Item Type:||Refereed Article|
|Keywords:||gene expression profiling, cDNA microarray, thyroid ophthalmopathy, Gravesí orbitopathy|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Ophthalmology and optometry|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Burdon, KP (Professor Kathryn Burdon)|
|Web of Science® Times Cited:||11|
|Deposited By:||Menzies Institute for Medical Research|
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