Fibroblast Growth Factor Receptor Inhibitors Reduce Adipogenesis of Orbital Fibroblasts and Enhance Myofibroblastic Differentiation in Graves' Orbitopathy
Journal
Ocular immunology and inflammation
Journal Volume
29
Journal Issue
1
Date Issued
2021-01-02
Author(s)
Shih, Chih-Wei
Lu, Ting-Xuan
Chou, Chien-Hsiang
Yen, Er-Yen
Chi, Yu-Chiao
Abstract
Purpose: Orbital fibroblasts are involved in pathogenesis of Graves' orbitopathy (GO). Fibroblast growth factor (FGF) affects fibroblasts of GO. This study aims to investigate the roles of FGF and FGF receptor (FGFR) in GO.Methods: Serum FGF proteins and orbital fibroblast FGFR proteins and mRNAs were measured in GO patients and controls. Orbital fibroblasts of GO were cultured and accessed for changes in proliferation (by nuclei number and MTT), myofibroblastic differentiation (by α-SMA), and adipogenesis (by oil droplets using Oil Red O stain) under FGF1 with or without FGFR inhibitors (FGFRi).Results: Serum FGF1 and FGF2 were increased in GO patients. FGFR1 was the most abundantly expressed FGFR in GO orbital fibroblasts. FGF1 increased GO fibroblast proliferation/adipogenesis and suppressed myofibroblastic differentiation, while FGFRi reversed these effects.Conclusion: FGF signaling may be involved in GO pathogenesis. Manipulation of FGF-FGFR pathway for GO treatment is worthy of further investigation.Registration number on Clinicaltrials.gov: NCT03324022.
Subjects
Adipogenesis; Graves’ orbitopathy; fibroblast growth factor receptors; fibroblast growth factors; myofibroblast
SDGs
Other Subjects
cyclosporine; fibroblast growth factor 1; fibroblast growth factor 2; fibroblast growth factor receptor 1; fibroblast growth factor receptor 2; fibroblast growth factor receptor 3; fibroblast growth factor receptor 4; immunoglobulin; messenger RNA; methyl
Type
journal article