Shyang-Rong Shih1,2,3, Shu-Lang Liao4,5, Chih-Wei Shih6, Yi-Hsuan Wei4, Ting-Xuan Lu7, Chien-Hsiang Chou7, Er-Yen Yen7, Yi-Cheng Chang2,8,9, Chia-Chi Lin10, Yu-Chiao Chi1,11, Wei-Shiung Yang2,11,12,13, Feng-Chiao Tsai2,7. 1. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 3. Center of Anti-Aging and Health Consultation, National Taiwan University Hospital, Taipei, Taiwan. 4. Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Ophthalmology, National Taiwan University College of Medicine, Taipei, Taiwan. 6. Department of Ophthalmology, Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan. 7. Department of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan. 8. Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan. 9. Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan. 10. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. 11. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 12. Center for Obesity, Lifestyle, and Metabolic Surgery, National Taiwan University Hospital, Taipei, Taiwan. 13. Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
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.
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 GOpatients 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 GOpatients. 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.