RBM47 as a potential therapeutic target for thyroid-associated ophthalmopathy

Abstract

RNA-binding motif 47 (RBM47) is a recently identified RNA-binding protein involved in early vertebrate development, immune homeostasis, and cancer development. This study examined the biological functions of RBM47 in thyroid-associated ophthalmopathy (TAO). Orbital fibroblasts (OFs) were obtained from the control (n = 6) and TAO groups (n = 6). Protein and gene expression in the obtained samples were investigated using immunohistochemistry, western blotting (WB), and RT-PCR. OFs with RBM47 knockdown were established using small interfering RNA. Subsequently, Oil Red O staining, WB, and RT-PCR were performed to assess adipogenesis in the OFs. The IL-1β-induced expression of proinflammatory molecules and hyaluronan (HA) was determined using enzyme-linked immunosorbent assay and RT-PCR. Moreover, TGF-β-induced fibrosis was evaluated using scratch assays, RT-PCR, and WB. RBM47 expression was markedly increased in orbital tissues and OFs obtained from individuals with TAO. RBM47 knockdown decreased adipogenesis and fibrosis in OFs, and downregulated the levels of insulin-like growth factor 1 receptor (IGF-1R), proinflammatory molecules, and HA. Furthermore, low RBM47 expression downregulated IGF-1R, which subsequently inhibited adipocyte differentiation by decreasing extracellular signal-regulated kinase signalling. These findings indicate that RBM47 may be involved in the regulation of adipogenesis, inflammation, HA production, and fibrosis, highlighting its potential of RBM47 as a therapeutic target for TAO.