Insulin-like growth factor-1 enhances the expression of functional TSH receptor in orbital fibroblasts from thyroid-associated ophthalmopathy |
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| Affiliation: | 1. Department of Ophthalmology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;2. Department of Ophthalmology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;3. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;3. Neurosurgery Department, Shiraz University of Medical Sciences, Shiraz, Iran;1. Unidad de Investigación Biomédica. Delegación Zacatecas. Instituto Mexicano del Seguro Social, IMSS, C.P. 98000, Mexico;2. Centro de Investigación en Ciencias de la Salud y Biomedicina. CICSaB Universidad Autónoma de San Luis Potosí, UASLP, C.P. 78000, Mexico;3. Unidad Regional de Reumatología y Osteoporosis Hospital Central Dr. Ignacio Morones Prieto. San Luis Potosí, SLP, C.P. 78290, Mexico;4. Cátedras CONACYT- Unidad de Investigación Biomédica de Zacatecas-IMSS, Zacatecas, C.P. 98000, Mexico;5. Facultad de Medicina y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Hospital Rural No. 51 IMSS Bienestar, Villanueva, Zacatecas, C.P. 99559, Mexico;1. Laboratory of Immunology of Microbial Aggression, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, 8380453, Chile;2. Laboratory of Biomedicine and Regenerative Medicine, Department of Clinical Sciences, Faculty of Veterinary and Animal Sciences, University of Chile, Santiago, 8820808, Chile;1. Department of Medicine - Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;2. Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children’s Hospital Boston, Harvard Medical School, Boston, MA, United States |
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| Abstract: | ![]()
Thyroid-associated ophthalmopathy (TAO), an autoimmune disease, occurs in approximately 50 % of patients with Graves’ hyperthyroidism. Thyroid-stimulating hormone receptor (TSHR) that is expressed in orbital fibroblasts is the autoimmune target in the development of TAO. In addition to thyroid-stimulating immunoglobulin (TSI), insulin-like growth factor (IGF)-1 is also involved in the development of TAO. IGF-1 has been reported to potentiate the effects of thyroid-stimulating hormone (TSH) and TSI on TSHR signaling. In the current study, we investigated the effects of IGF-1 on the cell surface expression of the functional TSHR and its possible mechanism of action in human orbital fibroblasts. Our results show that orbital fibroblasts from the TAO patients expressed higher levels of IGF-1 receptor (IGF-R), compared to control subjects. Treatment with IGF-1 enhanced the expression of surface TSHR in orbital fibroblasts from TAO patients, but not from control subjects. In addition, treatment with IGF-1 increased the level of TSHR at both the protein and mRNA levels. Furthermore, pre-treatment with IGF-1 potentiated TSH-induced cAMP production, compared to cells that were treated with only TSH. Our results also show that pre-treatment with cycloheximide, an inhibitor of mRNA translation, partially, but not completely, inhibited the expression of TSHR on the cell surfaces of orbital fibroblasts from TAO patients. These collective results show that IGF-1enhances the cell surface expression of functional TSHR, not only by increasing TSHR expression, but also by inducing TSHR translocation to the plasma membrane in orbital fibroblasts from TAO. |
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| Keywords: | Orbital fibroblasts Thyroid-associated ophthalmopathy IGF-1 Thyroid-stimulating hormone receptor |
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