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L. Van Steensel, J. Buth, D. Paridaens, W. van den Bosch, P. M. van Hagen, R. W. A. M. Kuijpers, H. Hooijkaas, W. A. Dik; Platelet-Derived Growth Factor-BB Enhances TSH Receptor Expression in Graves’ Ophthalmopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):824.
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Thyroid stimulating hormone receptor (TSHR) autoantibodies may play an important role in Graves’ophthalmopathy (GO), as illustrated by the association between clinical activity of GO and TSHR autoantibody levels. In addition, TSHR expression is elevated in GO orbital tissue. Although TSHR activation on orbital fibroblasts (OF) is thought to play a role in GO, the regulation of TSHR expression is largely unknown. Platelet-derived growth factor (PDGF) plays a major role in growth and remodeling of connective tissue and is highly expressed in GO orbital tissue. Here we investigated whether PDGF regulates TSHR expression by OF.
PDGF-B and TSHR mRNA levels in orbital tissues (GO and controls) were determined by RQ-PCR. Furthermore, the effect of PDGF-BB (50ng/ml) on TSHR mRNA and protein expression level by OF (GO and control derived) was determined by RQ-PCR, flowcytometry, immunohistochemistry and cell-based ELISA. Experiments using the PDGF-receptor tyrosine kinase inhibitor imatinib mesylate were performed to demonstrate involvement of PDGF-receptor signaling.
PDGF-B, but not TSHR, mRNA levels were significantly increased in orbital tissue from GO-patients. PDGF-B and TSH-R mRNA levels in orbital tissues correlated positively. PDGF-BB enhanced the TSHR expression by OF at the mRNA and protein level. Imatinib mesylate inhibited the effect of PDGF-BB on TSHR expression by OF.
The elevated PDGF-B mRNA expression in GO orbital tissue together with the positive correlation with TSHR mRNA levels and the enhanced TSHR expression by OF upon PDGF-BB stimulation implicates a role for PDGF-BB in increasing orbital TSHR expression in GO. This increased TSHR expression may enhance the vulnerability of OF to TSHR autoantibodies. We propose that the PDGF-system is a promising therapeutic target in GO (e.g with tyrosine kinase inhibitors).
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