Celecoxib and pioglitazone as potential therapeutics for regulating TGF-β-induced hyaluronan in dysthyroid myopathy
Journal
Investigative Ophthalmology and Visual Science
Journal Volume
57
Journal Issue
4
Pages
1951-1959
Date Issued
2016
Author(s)
Cheng, Anny M. S.
Yin, Han Y.
Chen, Angus
Chuang, Mei-Chun
He, Hua
Tighe, Sean
Sheha, Hosam
Abstract
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.
SDGs
Publisher
Association for Research in Vision and Ophthalmology Inc.
Type
journal article