|Title:||Celecoxib and Pioglitazone as Potential Therapeutics for Regulating TGF-beta-Induced Hyaluronan in Dysthyroid Myopathy||Authors:||Cheng, Anny M. S.
Yin, Han Y.
|Keywords:||cytokines;extraocular muscles;Graves' ophthalmopathy;hyaluronan;myoblast;transforming growth factor-beta||Issue Date:||2016||Journal Volume:||57||Journal Issue:||4||Start page/Pages:||1951-1959||Source:||Invest. Ophthalmol. Vis. Sci.||Abstract:||
PURPOSE. To investigate the role of extraocular muscles (EOM) myoblasts in Graves ophthalmopathy (GO) pathology and the effect of a cyclooxygenase (COX)-2 inhibitor and a peroxisome proliferator-activated receptor (PPAR)-gamma agonist in its treatment.
METHODS. Myoblasts were isolated and cultured from EOM of 10 patients with GO and 4 without (non-GO). The cultured myoblasts were treated with IFN-gamma, insulin-like growth factor (IGF)-1, IL-1 beta, and TNF-alpha, and the effect on PPAR-gamma, COX-2, TGF-beta, and thyroid stimulating hormone receptor (TSH-R) expressions were assessed using real-time (RT)-PCR, ELISA, and Western blot. The effect of a COX-2 inhibitor and a PPAR-gamma agonist on the expression of TGF-beta, hyaluronan synthases (HAS)-1, -2, and -3, and hyaluronan (HA) were further evaluated.
RESULTS. Real-time PCR showed significant upregulation in PPAR-gamma, COX-2, TGF-beta, and TSH-R mRNA expression in GO myoblasts when treated with TNF-alpha but not in the non-GO. While IFN-gamma and IGF-1 had no significant effect, IL-1 beta did upregulate COX-2 expression. These results were further confirmed by ELISA and Western blotting. Tumor necrosis factor alpha-induced TGF-beta in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2. The cyclooxygenase 2 inhibitor and PPAR-gamma agonist substantially diminished this TNF-alpha-induced TGF-beta, HA, and HAS3 expression.
CONCLUSIONS. These results demonstrate the role of EOM myoblasts in the pathogenesis of GO. The cyclooxygenase 2 inhibitor and PPAR-gamma agonist in this study are potential treatments for GO due to their ability to suppress TNF-alpha-induced TGF-beta, HAS, and HA upregulation.
|Appears in Collections:||分子醫學研究所|
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