Thy-1 Expression during 3T3-L1 Adipogenesis

 

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Introduction

Thy-1 (also known as CD90) is a small glycoprotein belonging to the immunoglobulin superfamily [1]. It is localized to lipid raft microdomains within the plasma membrane by virtue of a glycosyl phosphatidylinositol linkage. In mice, Thy-1 is predominantly expressed in T cells, thymocytes, neurons and bone marrow-derived stem cells [1] [2]. Although much is known about the structural properties of the Thy-1 molecule, very little is known about its function. Mice null for Thy-1 have only a subtle phenotype, including a neuronal defect in long-term potentiation, as well as enhanced T cell antigen receptor function [3] [4].

The human Thy-1 molecule has been identified as an inflammation-dependent adhesion molecule in endothelial cells, where it mediates interactions with monocytes, granulocytes, and melanoma cells [5] [6]. A role in adhesion was also suggested in studies using murine thymoma cells, in which they were reported to bind astrocytes in a Thy-1-dependent manner [7]. Thy-1 has been detected in human ovarian cells, and functional disruption of Thy-1 expression was noted in human ovarian cancer [8].

Recently, Thy-1 has been implicated in the adipogenic response of orbital fibroblasts. Approximately 50 % of these cells express Thy-1, so orbital fibroblasts are characterized as Thy-1(+) or Thy-1(-); this classification correlates with differences in cellular processes such as prostaglandin metabolism and glycosaminoglycan production [9]. Pathological expansion of the retroorbital contents occurs in Graves' ophthalmopathy due to excessive production of hydrophilic glycosaminoglycans, extraocular muscle hypertrophy, and/or adipose tissue accumulation [10]. A sub-population of orbital fibroblasts is actually preadipocytes, and can differentiate into adipocytes in primary culture when cued appropriately [11] [12]. Analysis of Thy-1 protein expression reveals that differentiated orbital adipocytes are all Thy-1(-), suggesting that the Thy-1(-) orbital fibroblasts are the actual preadipocytes [12]. When orbital fibroblasts are sorted by magnetic bead selection for Thy-1 surface display and then placed in culture, only Thy-1(-) cells acquire lipid droplets [13].

Since the orbital preadipocyte Thy-1 data may only be specific to this retroorbital depot, we have examined the relationship between Thy-1 expression in an established and more generalized model of adipogenesis - the murine 3T3-L1 adipocyte.

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Dr. A. Sorisky

Ottawa Health Research Institute

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