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Anny M. S. Cheng, Han Y. Yin, Angus Chen, Ya-Wen Liu, Mei-Chun Chuang, Hua He, Sean Tighe, Hosam Sheha, Shu-Lang Liao; Celecoxib and Pioglitazone as Potential Therapeutics for Regulating TGF-β–Induced Hyaluronan in Dysthyroid Myopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(4):1951-1959. doi: 10.1167/iovs.15-18018.
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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)-γ agonist in its treatment.
Myoblasts were isolated and cultured from EOM of 10 patients with GO and 4 without (non-GO). The cultured myoblasts were treated with IFN-γ, insulin-like growth factor (IGF)-1, IL-1β, and TNF-α, and the effect on PPAR-γ, COX-2, TGF-β, 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-γ agonist on the expression of TGF-β, hyaluronan synthases (HAS)-1, -2, and -3, and hyaluronan (HA) were further evaluated.
Real-time PCR showed significant upregulation in PPAR-γ, COX-2, TGF-β, and TSH-R mRNA expression in GO myoblasts when treated with TNF-α but not in the non-GO. While IFN-γ and IGF-1 had no significant effect, IL-1β did upregulate COX-2 expression. These results were further confirmed by ELISA and Western blotting. Tumor necrosis factor α–induced TGF-β in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2. The cyclooxygenase 2 inhibitor and PPAR-γ agonist substantially diminished this TNF-α–induced TGF-β, HA, and HAS3 expression.
These results demonstrate the role of EOM myoblasts in the pathogenesis of GO. The cyclooxygenase 2 inhibitor and PPAR-γ agonist in this study are potential treatments for GO due to their ability to suppress TNF-α–induced TGF-β, HAS, and HA upregulation.
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