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Altered ganglioside expression modulates the pathogenic mechanism of thyroid-associated ophthalmopathy by increase in hyaluronic acid.

Authors
Kook, KH; Choi, YH; Kim, YR; Park, SJ; Jou, I; Kim, SJ; Lee, SY
Citation
Investigative ophthalmology & visual science, 52(1):264-273, 2011
Journal Title
Investigative ophthalmology & visual science
ISSN
0146-04041552-5783
Abstract
PURPOSE: The aim of this study was to determine the role of gangliosides in pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO).



METHODS: The gangliosides profile and mRNA level of sialyltransferases of the orbital tissues from TAO patients (n = 5) and non-TAO subjects (n = 4) were investigated. In addition, the effect of exogenous gangliosides on the expression of hyaluronic acid was examined in orbital fibroblasts. For in vitro experiments, we used four different strains of cells obtained from non-TAO subjects with at least three replicates for each strain.



RESULTS: Trisialoganglioside 1b (GT1b) was significantly overexpressed in the orbital tissue of TAO patients compared with control tissue, whereas no significant difference was observed for either monosialoganglioside 1 (GM1) or disialoganglioside 1a (GD1a) by digital analyses of immunohistochemical images. Moreover, mRNA levels of sialyltransferase (SAT)-I and SAT II were increased in TAO patients compared with control. Exogenous GT1b strongly induced the morphologic changes related to an accumulation of sparse flocculent precipitates in lysosomes and increased the extracellular hyaluronic acid level in orbital fibroblasts with the induction of hyaluronic acid synthase, which were less by GD1a but not by GM1. The GT1b-induced morphologic changes of cells were due, at least in part, to an increase of intracellular hyaluronic acid. Co-treatment of hyaluronidase nicely attenuated the morphologic changes in orbital fibroblasts. Thy-1(+) orbital fibroblasts were more capable of producing hyaluronic acid by exogenous GT1b.



CONCLUSIONS: The results suggest that gangliosides, particularly GT1b, may play a role in the pathologic mechanisms of TAO by stimulating an increase in hyaluronic acid.
MeSH terms
AdultAntigens, CD/geneticsCells, CulturedEnzyme-Linked Immunosorbent AssayFemaleFibroblasts/metabolismFluorescent Antibody Technique, IndirectG(M1) Ganglioside/physiologyGangliosides/*physiologyGraves Ophthalmopathy/*etiology/metabolismHumansHyaluronic Acid/*metabolismMaleMiddle AgedOrbit/metabolism/pathologyRNA, Messenger/geneticsReverse Transcriptase Polymerase Chain ReactionSialyltransferases/genetics
DOI
10.1167/iovs.10-5276
PMID
20811057
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Ophthalmology
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
국, 경훈박, 수정주, 일로
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