Altered ganglioside expression modulates the pathogenic mechanism of thyroid associated ophthalmopathy by increase in hyaluronic acid.
Summary of "Altered ganglioside expression modulates the pathogenic mechanism of thyroid associated ophthalmopathy by increase in hyaluronic acid."
Purpose: The aim of this study was to determine the role of gangliosides in pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO). Methods: We investigated the gangliosides profile and mRNA level of sialyltransferases of the orbital tissues from TAO patients (n=5) and non-TAO subjects (n=4). 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 to control tissue, while 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 I (SAT I) and SAT II were increased in TAO patients compared to 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 and not by GM1. The GT1b-induced morphological changes of cells were due, at least in part, to an increase of intracellular hyaluronic acid. And co-treatment of hyaluronidase nicely attenuated the morphological changes in orbital fibroblasts. Thy-1+ orbital fibroblasts were more capable of producing hyaluronic acid by exogenous GT1b. Conclusions: Our results suggest that gangliosides, particularly GT1b, may play a role in the pathologic mechanisms of TAO by stimulating an increase in hyaluronic acid.
Affiliation
Ophthalmology, Ajou University School of Medicine, Suwon, Korea, Republic of.
Journal Details
This article was published in the following journal.
Name: Investigative ophthalmology & visual science
ISSN: 1552-5783
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20811057
- DOI: http://dx.doi.org/10.1167/iovs.10-5276
Medical and Biotech [MESH] Definitions
G(m3) Ganglioside
A ganglioside present in abnormally large amounts in the brain and liver due to a deficient biosynthetic enzyme, G(M3):UDP-N-acetylgalactosaminyltransferase. Deficiency of this enzyme prevents the formation of G(M2) ganglioside from G(M3) ganglioside and is the cause of an anabolic sphingolipidosis.
Immunoglobulins, Thyroid-stimulating
Autoantibodies that bind to the thyroid-stimulating hormone (TSH) receptor (RECEPTORS, THYROTROPIN) on thyroid epithelial cells. The autoantibodies mimic TSH causing an unregulated production of thyroid hormones characteristic of GRAVES DISEASE.
Lingual Thyroid
A condition characterized by the presence of rudimentary THYROID tissue at the base of the TONGUE. It is due to failed embryonic development and migration of thyroid tissue to its normal location. The lingual thyroid usually cannot maintain adequate hormone production thereby resulting in HYPOTHYROIDISM.
Doxepin
A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.
Hyperthyroidism
Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.
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