Association of fibroblast growth factor 10 with the fibrotic and inflammatory pathogenesis of Graves’ orbitopathy

Abstract

Purpose The role of fibroblast growth factor (FGF) in orbital fibroblasts (OFs) is rarely known. In this study, we investigated the effect of FGF10 on fibrosis and the inflammation mechanism of Graves′ orbitopathy (GO). Methods Orbital tissue from GO (n = 15) and non-GO (n = 15) was obtained for this study. The mRNA and protein expression levels of FGF10 and FGF receptor 2b (FGFR2b) in orbital tissue were determined by real-time polymerase chain reaction, western blot analysis, and confocal microscopy. The effects of FGF10 on transforming growth factor (TGF)-β1 induced fibrotic proteins and interleukin (IL)-1β- or tumor necrosis factor (TNF)-α- induced inflammatory proteins were investigated using recombinant human (rh) FGF10 and small interfering (si) RNA transfection against FGF10. Results FGF10 and FGFR2b mRNA expression levels were significantly lower in GO orbital tissues than in non-GO orbital tissues (p = 0.009 and 0.005, respectively). Immunostaining of FGF10 in orbital adipose tissues showed differences in FGF10 expression between GO and control samples. Immunostaining of FGF10 was very weak in the orbital tissues of GO patients. TGF-β1-induced fibronectin, collagen Iα, α-smooth muscle actin protein expression in GO OFs was attenuated by rhFGF10 treatment and increased by knockdown of FGF10 via siFGF10 transfection. Similarly, IL-1β- or TNF-α-induced IL-6, IL-8, and cyclooxygenase-2 protein production in GO OFs was either blocked by rhFGF10 treatment or further upregulated by inhibition of FGF10 via siFGF10 transfection. Conclusions Our data demonstrate that FGF10 has beneficial effects on the inflammatory and fibrotic mechanisms of GO in primary cultured OFs, providing new insights into GO pathology and the discovery of FGF10 as a promising novel therapeutic application for the treatment of GO.

Expression levels of RUNX3 and FGFR2 in peripheral blood of severe acute pancreatitis and their clinical significance

“…As known before, the maternally expressed gene 3/miR-195-5p/ FGFR2 axis mitigates inflammatory injury in caerulein-induced pancreatic cells by inactivating nuclear factor-kappa beta [ 12 ]. Likewise, blocking the FGF10/ FGFR2b upregulates the release of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL) 6, and IL-8 in orbital fibroblasts [ 30 ]. Furthermore, the JASPAR database and the ChIP assay confirmed the binding relationship between RUNX3 and the FGFR2 promoter, and Pearson correlation analysis revealed a positive correlation between RUNX3 expression and FGFR2 expression in peripheral blood of SAP patients, suggesting that RUNX3 may bind to the FGFR2 promoter to upregulate FGFR2 transcription and then play a role in SAP.…”

Polyphenol Extracts From Germinated Mung Beans Can Improve Type 2 Diabetes in Mice by Regulating Intestinal Microflora and Inhibiting Inflammation

“…Diabetic patients will produce chronic inflammation in the body. TNF-α, IL-6, and IL-10 are inflammatory factors secreted by inflammatory cells ( 37 ). TNF-α, as the earliest inflammatory factor in the process of body inflammatory, plays an important role in glycoprotein signal transduction and synthesis.…”

The Effect of Rho Kinase Inhibitors on In Vitro Human Orbital Preadipocytes

“…Fibroblast between the second and fifth passages were used for analysis. [20][21][22][23] For adipogenesis, cells were cultured in serum-free DMEM supplemented with T3, insulin (Boehringer-Mannheim, Mannheim, Germany), carbaprostaglandin (cPGI2; Calbiochem, La Jolla, CA, U.S.A.), and dexamethasone. A peroxisome proliferator-activated receptor gamma agonist, rosiglitazone (10 μM; Cayman, Ann Arbor, MI, U.S.A.), was also added from day 1 of differentiation for heightened stimulation of adipogenesis.…”