Abstract
Background and Aims: Fat accumulation and fibrosis are the hallmarks of chronic phase of Graves ophthalmopathy (GO) and of arm lymphedema. The aim of this study was to examine common pathogenetic mechanisms that contribute to the development of GO and lymphedema.
Methods: Subcutaneous adipose/connective tissue was obtained from the lympadematous arm of ten patients with chronic arm lymphedema, control tissue was collected simultaneously from the unaffected arm of the same ten individuals. Intraorbital adipose/connective tissue was collected from ten patients with chronic GO and ten thyroid-healthy controls undergoing restorative eyelid surgery. Gene expression analysis was performed using the HG-U133 Plus 2.0 GeneChip from Affymetrix. Results were confirmed with real-time RT-PCR.
Results: 36 genes were upregulated (fold change >2) and 5 genes downregulated (fold change > 2) in the lymphedema arm compared to the healthy arm.14 genes were upregulated (fold change > 2) and 33 genes downregulated (fold change > 2) in chronic GO compared to controls. SFRP2, ABCG1 and CPXM1 were upregulated in both conditions and have known functions in the Wnt pathway, differentiation, proliferation, adhesion, inflammation and steroid metabolism. The other genes differentially expressed between lymphedema arm and healthy arm were mostly involved in differentiation, development, fibrosis, wound healing, extracellular matrix composition and remodeling, fat metabolism and inflammation. The other genes differentially expressed between chronic GO and controls had role in immune response, fat metabolism and inflammation.
Conclusions: This is the first study that compares expression profiles of chronic GO and lymphedema. We have established a model where some of the pathogenetic mechanisms of GO can be studied in a more easily accessible tissue, chronic lymphedema. Three genes, SFRP2, ABCG1 and CPXM1, were overexpressed in both tissues and have functions that may be of importance in the chronic phase of GO.