Evidence for enhanced Thy-1 (CD90) expression in orbital fibroblasts of patients with Graves' ophthalmopathy

Teck Kim Khoo, Michael J. Coenen, A. Reagan Schiefer, Seema Kumar, Rebecca S. Bahn

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: Thy-1 is a surface protein that defines functionally distinct subpopulations of fibroblasts, with those lacking the antigen being capable of adipogenesis. Because increased fat cell development is a hallmark of the orbit in Graves' ophthalmopathy (GO), we wished to compare baseline Thy-1 expression in orbital fibroblasts from GO patients and normal individuals, and determine whether levels of the protein might be impacted by adipogenesis following peroxisome proliferator activator-γ ligation. Methods: Orbital adipose/connective tissue specimens were obtained from euthyroid patients undergoing orbital decompression surgery for severe GO (n = 9) and from normal individuals (n = 9). Thy-1 mRNA and protein levels were assessed in tissue specimens and in orbital fibroblast cultures at baseline using RT-PCR, quantitative immunofluorescent staining, and flow cytometry using a specific Thy-1 mouse anti-human CD90/Thy-1 monoclonal antibody. In addition, some orbital fibroblast cultures were treated with rosiglitazone (1 μL/mL; 2 nM) or control for 10 days in culture. Results: We found that Thy-1 mRNA and protein expression was higher in uncultured GO connective/adipose tissue specimens (3.8-fold; 0.835 ± 0.116 relative expression) compared with normal (0.22 ± 0.062; p = 0.002) and in cultured orbital fibroblasts from GO patients (3.3-fold; 9.28 ± 1.82 relative expression) compared with normal cultures (2.80 ± 0.42; p = 0.013). Adipocyte differentiation had no effect on Thy-1 expression. Flow cytometry and immunofluorescent staining showed increased numbers of Thy-1-positive cells in the GO (mean 77.9 + 4.09%; range 66.5-84.8%) compared with the normal fibroblast cultures (66.8 + 1.6%; range 63.3-71.0% positive; p = 0.046), as well as higher levels of expression on the positive cells. Conclusions: Increased Thy-1 expression in GO orbital tissues and cultures is likely a consequence of the orbital disease process, reflecting both the presence of increased numbers of Thy-1-positive cells and higher expression on those cells. Adipogenesis itself does not appear to impact Thy-1 expression. Increased expression of this protein in GO could represent an adaptive response to cell injury, in effect limiting disease progression within the orbital adipose/connective tissues.

Original languageEnglish (US)
Pages (from-to)1291-1296
Number of pages6
JournalThyroid
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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