Evidence for Enhanced Thy-1 (CD90) Expression in Orbital Fibroblasts of Patients with Graves' Ophthalmopathy

Khoo, Teck Kim; Coenen, Michael J.; Schiefer, Alfred; Kumar, Seema; Bahn, Rebecca S.

doi:10.1089/thy.2008.0255

Cited by 47 publications

(38 citation statements)

References 14 publications

(17 reference statements)

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“…This mechanism of lipid accumulation is distinct from that of adipocytes (37) and keratinocytes (32), and demonstrates the unique biology of the Thy-1 (1) lipofibroblast. Pulmonary fibroblasts seem to have biological characteristics distinct from myometrial or orbital fibroblasts, because the expression of Thy-1 in those tissues does not seem to stimulate lipid accumulation (46)(47)(48). A schematic depiction of the proposed mechanism for lipid accumulation in Thy-1 (1) pulmonary lipofibroblasts is presented in Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Varisco

Ambalavanan

Whitsett

et al. 2012

Am J Respir Cell Mol Biol

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Thy-1 is a glycosylphosphytidylinositol-linked cell-surface glycoprotein present on a subset of lung fibroblasts, which plays an important role in postnatal alveolarization. In the present study, we define the role of Thy-1 in pulmonary lipofibroblast differentiation and in the regulation of lipid homeostasis via peroxisome proliferator-activated receptor-g (PPARg). Thy-1 was associated with interstitial cells containing lipid droplets in vivo. The transfection of Thy-1 into Thy-1 (2) fibroblasts increased triglyceride content, fatty-acid uptake, and the expression of the lipofibroblast marker adipocyte differentiationrelated protein. Thy-1 (1) fibroblasts exhibited 2.4-fold higher PPARg activity, and the inhibition or activation of PPARg reduced and increased triglyceride content, respectively. Thy-1 (2) fibroblasts were not responsive to either of the PPARg agonists ciglitazone or prostaglandin J 2 , supporting the importance of Thy-1 in signaling via PPARg. Thy-1 (1) fibroblasts expressed significantly higher concentrations of fatty-acid transporter protein-3 mRNA, and demonstrated higher rates of fatty-acid uptake and increased triglyceride content. The inhibition of fatty-acid transporter protein function reduced Thy-1 (1) fibroblast lipid content. The expression of Thy-1 in C57BL/6 lung fibroblasts increased during the neonatal period, coinciding with the onset of alveolarization. Thy-1 promoted lipofibroblast differentiation via the expression of PPARg, stimulated lipid accumulation via fatty-acid esterification, and enhanced the fatty-acid uptake mediated by fattyacid transporter proteins. Thy-1 is important in the regulation of lipofibroblast differentiation in the developing lung.Keywords: Thy-1; lipofibroblast; PPARg; lipid metabolismBeginning at 35 weeks after conception and continuing for up to 8 years after birth, the alveolar stage of lung development is marked by the sequential division of larger airspaces into smaller ones by secondary alveolar septa (1, 2). From term birth until adulthood, the 5-fold increase in the number of alveoli and the 20-fold increase in alveolar surface area are critical in meeting the increasing oxygenation and ventilation needs of human growth and activity (2, 3). Premature birth, exposure to high concentrations of inspired oxygen, and mechanical ventilation lead to impaired alveolar development and chronic lung disease (4). The impaired lung function of chronic lung disease results in significant morbidity, mortality, and healthcare costs from early life through adulthood (5-8). Understanding how the different tissues of the lung behave during normal and impaired alveolar development is a key first step toward restoring alveolarization and attenuating the burden of respiratory disease after premature birth.Pulmonary lipofibroblasts comprise an incompletely characterized population of lipid-containing interstitial cells that play an important role in alveolarization. Hyperoxia, hypoxia, and nicotine exposure stimulate lipofibroblasts to myofibroblast differentiation a...

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Section: Discussionmentioning

confidence: 99%

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Varisco

Ambalavanan

Whitsett

et al. 2012

Am J Respir Cell Mol Biol

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“…It has been well described that fibroblasts are heterogeneous, differing not only between organ systems but also within a given organ (25,(65)(66)(67)(68). We previously published that fibroblasts from the lung exhibit significant interindividual variability in their apoptotic response to cigarette smoke (69), a finding that may explain why only a fraction of smokers develop lung diseases, such as chronic obstructive pulmonary disease.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell-derived Prostaglandin D2 Controls Hyaluronan Synthesis in Human Orbital Fibroblasts via DP1 Activation

Guo

Baglole

O’Loughlin

et al. 2010

Journal of Biological Chemistry

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Thyroid eye disease (TED) is a debilitating disorder characterized by the accumulation of adipocytes and hyaluronan (HA).Production of HA by fibroblasts leads to remarkable increases in tissue volume and to the anterior displacement of the eyes. Prostaglandin D 2 (PGD 2 ), mainly produced by mast cells, promotes orbital fibroblast adipogenesis. The mechanism by which PGD 2 influences orbital fibroblasts and their synthesis of HA is poorly understood. We report here that mast cell-derived PGD 2 is a key factor that promotes HA biosynthesis by orbital fibroblasts. Primary orbital fibroblasts from TED patients were isolated and used to test the effects of PGD 2 , prostaglandin J 2 , as well as prostaglandin D receptor (DP) agonists and antagonists on HA synthesis. The expression of HA synthase (HAS), hyaluronidase, DP1, and DP2 mRNA levels was assessed by PCR. Small interfering RNAs against HAS1 or HAS2 were used to assess the importance

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“…Valuesa are means ϩ SD, n ϭ 40; **P Ͻ 0.01. al. (21) published the results of a study in which they found Thy-1 mRNA and protein expression to be higher in orbital tissues and fibroblasts from TED patients compared with those from normal individuals. Therefore, TED patients are not at risk for increased orbital adipogenesis because of a deficiency of Thy-1-positive orbital fibroblasts.…”

Section: C677mentioning

confidence: 99%

Novel anti-adipogenic activity produced by human fibroblasts

Lehmann¹,

Woeller²,

Pollock³

et al. 2010

American Journal of Physiology-Cell Physiology

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Fatty tissue is generally found in distinct “depots” distributed throughout the human body. Adipocytes from each of the various depots differ in their metabolic capacities and their responses to environmental stimuli. Although a general understanding of the factors responsible for adipogenic transformation has been achieved, much is not understood about the mechanisms of adipose tissue deposition and the phenotypes of the adipocytes found within each depot. A clue to the factors regulating fat deposition may come from studies of adipogenesis using primary human orbital fibroblasts from patients with thyroid eye disease, a condition in which intense inflammation leads to expansion of orbital adipose tissue via differentiation of fibroblasts to adipocytes. We have previously demonstrated that adipogenesis of orbital fibroblasts is negatively correlated with cellular expression of the Thy-1 surface marker. In this study, we developed a novel imaging flow cytometric approach for the assessment of adipogenesis to test the hypothetical dependence of adipogenic potential on lack of Thy-1 expression. Using this technique, we learned that Thy-1-positive fibroblasts are, in fact, capable of differentiating into adipocytes but are less likely to do so because they secrete a paracrine anti-adipogenic factor. It is possible that such a factor plays an important role in the prevention of excess fat deposition in the normal orbit and may even be exploited as a therapy for the treatment of obesity, a major worldwide health concern.

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Evidence for Enhanced Thy-1 (CD90) Expression in Orbital Fibroblasts of Patients with Graves' Ophthalmopathy

Cited by 47 publications

References 14 publications

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Mast Cell-derived Prostaglandin D2 Controls Hyaluronan Synthesis in Human Orbital Fibroblasts via DP1 Activation

Novel anti-adipogenic activity produced by human fibroblasts

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