transforming-growth-factor-beta and Graves-Ophthalmopathy

transforming-growth-factor-beta has been researched along with Graves-Ophthalmopathy* in 16 studies

Other Studies

16 other study(ies) available for transforming-growth-factor-beta and Graves-Ophthalmopathy

ArticleYear
The miR-103a-3p/TGFBR3 axis regulates TGF-β-induced orbital fibroblast activation and fibrosis in thyroid-eye disease.
    Molecular and cellular endocrinology, 2023, 01-01, Volume: 559

    Molecular pathways that contribute to orbital fibroblast activation during thyroid-eye disease (TED) may promote TED progression. Non-coding RNAs, especially miRNAs, play a critical role in the pathogenesis of TED. In the present study, miR-103a-3p was dramatically upregulated and TGFBR3 was downregulated within TED orbital tissue samples and TGF-β-stimulated TED orbital fibroblasts. miR-103a-3p inhibition in TGF-β-stimulated TED orbital fibroblasts partially abolished TGF-β-induced fibrotic alterations, as manifested by the impaired fibroblast cell viability and decreased vimentin and fibronectin levels. miR-103a-3p directly targeted TGFBR3 in TED orbital samples and TGF-β-stimulated TED orbital fibroblasts. In TGF-β-stimulated TED orbital fibroblasts, TGFBR3 overexpression inhibited fibroblast cell viability and decreased vimentin and fibronectin levels. TGFBR3 overexpression partially attenuated the inhibitory effects of miR-103a-3p overexpression on TGFBR3 expression and the promotive effects of miR-103a-3p overexpression on TGF-β-induced fibrotic alterations. Under TGF-β stimulation, miR-103a-3p overexpression significantly promoted, whereas TGFBR3 overexpression inhibited the phosphorylation of Erk1/2, JNK, Smad2, and Smad3. TGFBR3 overexpression also partially abolished the effects of miR-103a-3p overexpression on Erk1/2, JNK, Smad2, and Smad3 phosphorylation. In conclusion, the miR-103a-3p/TGFBR3 axis regulated TGF-β-induced TED orbital fibroblast activation and fibrosis in TED, with the possible involvement of the Erk/JNK and TGF-β/Smad signaling pathways.

    Topics: Cell Proliferation; Fibroblasts; Fibronectins; Fibrosis; Graves Ophthalmopathy; Humans; MicroRNAs; Transforming Growth Factor beta; Vimentin

2023
Ceruloplasmin regulating fibrosis in orbital fibroblasts provides a novel therapeutic target for Graves' orbitopathy.
    Journal of endocrinological investigation, 2023, Volume: 46, Issue:10

    In diagnosing the pathogenesis of Graves' orbitopathy (GO), there is a growing interest in fibrosis generated by orbital fibroblasts (OFs); nevertheless, the involvement of ceruloplasmin (CP) in OFs remains unknown.. Differentially expressed genes (DEGs) were identified through bioinformatic analysis. OFs were isolated from orbital tissue and identified with immunofluorescent staining. The levels of DEGs were validated in GO tissue samples and TGF-β-challenged OFs, and CP was selected for the following laboratory investigations. CP overexpression or knockdown was achieved, and cell viability and fibrosis-associated proteins were investigated to assess the cell phenotype and function. Signaling pathways were subsequently investigated to explore the mechanism of CP function in OFs.. CP and cathepsin C (CTSC) are two overlapped DEGs in GSE58331 and GSE105149. OFs were isolated and identified through fibrotic biomarkers. CP and CTSC were downregulated in GO tissue samples and TGF-β-challenged OFs. CP overexpression or knockdown was achieved in OFs by transducing a CP overexpression vector or small interfering RNA against CP (si1-CP or si2-CP) and verified using a qRT-PCR. CP overexpression inhibited cell viability and reduced the levels of α-SMA, vimentin, fibronectin, and collagen I, whereas CP knockdown exerted opposite effects on OFs. CP overexpression inhibited the phosphorylation of Smad3, Erk1/2, p38, JNK, and AKT; conversely, CP knockdown exerted opposite effects on the phosphorylation of factors mentioned above.. CP was downregulated in GO and suppressed the expression of fibrosis-associated proteins in both GO and normal OFs. CP might serve as a promising therapeutic agent in the treatment regimens for GO.

    Topics: Cells, Cultured; Ceruloplasmin; Fibroblasts; Fibrosis; Graves Ophthalmopathy; Humans; Transforming Growth Factor beta

2023
RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.
    Journal of translational medicine, 2023, 06-18, Volume: 21, Issue:1

    Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-β-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-β-induced cell viability, decreased TGF-β-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-β-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-β, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.

    Topics: Animals; Aptamers, Nucleotide; CD40 Antigens; CD40 Ligand; Collagen; Fibroblasts; Graves Ophthalmopathy; Mice; NF-kappa B; Orbit; Transforming Growth Factor beta

2023
Botox-A improve the thyroid-associated ophthalmopathy (TAO) orbital fibroblast activation through inhibiting the TGF-β/Smad signaling.
    Experimental eye research, 2022, Volume: 217

    The activation of orbital fibroblasts can result in fibrosis, finally contributing to thyroid-associated ophthalmopathy (TAO) progression. Although the effect of BTX-A on the treatment of TAO-related strabismus and upper eyelid retraction has long been recognized in clinical work, the underlying mechanism of BTX-A improving TAO-related strabismus and upper eyelid retraction has not been uncovered yet. In the present study, we successfully isolated and authenticated normal and TAO orbital fibroblasts. Compared with PBS, BTX-A and TACA exerted similar inhibitory effects on TAO orbital fibroblast proliferation and ECM production. TGF-β stimulation induced the proliferation and ECM production by TAO orbital fibroblast, which was significantly inhibited by BTX-A or TACA treatment. Under TGF-β stimulation, the inhibitory effects of BTX-A or TACA treatment on TAO orbital fibroblast proliferation and ECM production were reversed by TGF-β/Smad signaling agonist SRI-011381. Collectively, BTX-A inhibited TGF-β-induced TAO orbital fibroblast activation through inhibiting the TGF-β/Smad signaling. Considering that TACA shows no satisfactory curative effects on symptoms closely related to the function of extraocular muscles, such as eye movement and diplopia, BTX-A might be a promising agent in TAO treatment.

    Topics: Botulinum Toxins, Type A; Fibroblasts; Graves Ophthalmopathy; Humans; Orbit; Strabismus; Transforming Growth Factor beta

2022
TGFβ-Treated Placenta-Derived Mesenchymal Stem Cells Selectively Promote Anti-Adipogenesis in Thyroid-Associated Ophthalmopathy.
    International journal of molecular sciences, 2022, May-17, Volume: 23, Issue:10

    Orbital fibroblasts (OFs) in thyroid-associated ophthalmopathy (TAO) are differentiated from pre-adipocytes and mature adipocytes; increased lipid and fat expansion are the major characteristics of ophthalmic manifestations. Human placental mesenchymal stem cells (hPMSCs) were reported to immunomodulate pathogenesis and suppress adipogenesis in TAO OFs. Here, we prepared transforming growth factor β (TGFβ, 20 ng/mL)-treated hPMSCs (TGFβ-hPMSCs) in order to enhance anti-adipogenic effects in vitro and in TAO mice. TAO OFs were grown in a differentiation medium and then co-cultured with hPMSCs or TGFβ-hPMSCs. TAO OFs were analyzed via quantitative real-time polymerase chain reaction, Oil red O staining, and western blotting. The results showed that TGFβ-hPMSCs reduced the expression of adipogenic, lipogenic, and fibrotic genes better than hPMSCs in TAO OFs. Moreover, the adipose area decreased more in TAO mice injected with TGFβ-hPMSCs compared to those injected with hPMSCs or a steroid. Further, TGFβ-hPMSCs inhibited inflammation as effectively as a steroid. In conclusion, TGFβ-hPMSCs suppressed adipogenesis and lipogenesis in vitro and in TAO mice, and the effects were mediated by the SMAD 2/3 pathways. Furthermore, TGFβ-hPMSCs exhibited anti-inflammatory and anti-fibrotic functions, which suggests that they could be a new and safe method to promote the anti-adipogenic function of hPMSCs to treat TAO patients.

    Topics: Adipogenesis; Animals; Female; Graves Ophthalmopathy; Humans; Mesenchymal Stem Cells; Mice; Placenta; Pregnancy; Transforming Growth Factor beta

2022
Potential Therapeutic Role of Bone Morphogenic Protein 7 (BMP7) in the Pathogenesis of Graves' Orbitopathy.
    Investigative ophthalmology & visual science, 2022, 06-01, Volume: 63, Issue:6

    We investigated a role of bone morphogenic protein 7 (BMP7), a member of the TGF-β superfamily on pathogenic mechanism of Graves' orbitopathy (GO). The therapeutic effects of BMP7 on inflammation and fibrosis were evaluated in cultured Graves' orbital fibroblasts.. Expression of BMP7 was compared in cultured orbital tissue explants from GO (n = 12) and normal control (n = 12) subjects using real-time PCR. Orbital fibroblasts were cultured from orbital connective tissues obtained from GO (n = 3) and normal control patients (n = 3). Cells were pretreated with recombinant human BMP7 (rhBMP7) before stimulation with TGF-β, IL-1β, and TNF-α. Fibrosis-related proteins and inflammatory cytokines were analyzed by Western blotting. The activation of signaling molecules in inflammation and fibrosis was also analyzed.. The expressions of BMP7 mRNA were lower in GO orbital tissues than control. Fibrosis-related proteins, fibronectin, collagen 1α, and α-SMA induced by TGF-β were suppressed by treating rhBMP7, and rhBMP7 upregulated TGF-β induced SMAD1/5/8 protein expression, whereas downregulated SMAD2/3. Increased pro-inflammatory molecules, IL-6, IL-8, and intercellular adhesion molecule-1 (ICAM-1) by IL-1β or TNF-α were blocked by rhBMP7 treatment, and the expression of phosphorylated NFκB and Akt was suppressed by rhBMP7 treatment.. BMP7 transcript levels were downregulated in Graves' orbital tissues. Exogenous BMP7 treatment showed inhibitory effects on the production of profibrotic proteins and proinflammatory cytokines in orbital fibroblasts. Our results provide a molecular basis of BMP7 as a new potential therapeutic agent through the opposing mechanism of profibrotic TGF-β/SMAD signaling and proinflammatory cytokine production.

    Topics: Bone Morphogenetic Protein 7; Cells, Cultured; Cytokines; Fibroblasts; Fibrosis; Graves Ophthalmopathy; Humans; Inflammation; Orbit; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

2022
Potential Therapeutic Activity of Berberine in Thyroid-Associated Ophthalmopathy: Inhibitory Effects on Tissue Remodeling in Orbital Fibroblasts.
    Investigative ophthalmology & visual science, 2022, 09-01, Volume: 63, Issue:10

    Berberine (BBR), an alkaloid produced by a traditional Chinese plant, was recently attributed multiple effects on lipometabolism, inflammation, and fibrosis. Thyroid-associated ophthalmopathy (TAO) is highly associated with these pathologic changes. Thus, we aimed to examine the potential therapeutic effect of BBR in an in vitro model of TAO.. Orbital fibroblasts (OFs) obtained from control donors (n = 6) or patients with TAO (n = 6) were cultured. The CCK-8 assay was conducted for assessing the optimal concentration range. Oil Red O staining, Western blotting, and quantitative RT-PCR (qRT-PCR) were conducted to assess adipogenesis in OFs. RNA sequencing (RNA-seq) was used to screen the key pathways of the antiadipogenic effect mediated by BBR. Along with incremental concentrations of BBR, IL-1β-induced expression of proinflammatory molecules was determined by ELISA and qRT-PCR. In addition, TGF-β-induced hyaluronan (HA) production and fibrosis were evaluated by ELISA, qRT-PCR, and Western blotting.. TAO-OFs, but not control fibroblasts (CON-OFs), were readily differentiated into adipocytes with the commercial medium. Intracellular lipid accumulation was dose-dependently decreased by BBR, and adipogenic markers were also downregulated. Moreover, the PPARγ and AMPK pathways were screened out by RNA-seq and their downstream effectors were suppressed by BBR. Besides, BBR attenuated IL-1β-induced expression of proinflammatory molecules in both TAO-OFs and CON-OFs by blocking nuclear factor-κB signaling. BBR's inhibitory effect on TGF-β-mediated tissue remodeling was also confirmed in OFs.. These findings demonstrate BBR has outstanding capabilities of controlling adipogenesis, inflammation, HA production, and fibrosis in OFs, highlighting its potential therapeutic role in TAO management.

    Topics: Berberine; Fibroblasts; Fibrosis; Graves Ophthalmopathy; Humans; Hyaluronic Acid; Inflammation; Orbit; Transforming Growth Factor beta

2022
Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves' Ophthalmopathy-Derived Orbital Fibroblasts
    Frontiers in endocrinology, 2020, Volume: 11

    Topics: Adult; Amides; Cell Differentiation; Female; Fibrosis; Graves Ophthalmopathy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; MAP Kinase Signaling System; Middle Aged; Myofibroblasts; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Primary Cell Culture; Pyridines; rho-Associated Kinases; rhoA GTP-Binding Protein; Simvastatin; Transforming Growth Factor beta

2020
Proton pump inhibitors attenuate myofibroblast formation associated with thyroid eye disease through the aryl hydrocarbon receptor.
    PloS one, 2019, Volume: 14, Issue:9

    Thyroid eye disease (TED) can lead to scar formation and tissue remodeling in the orbital space. In severe cases, the scarring process leads to sight-threatening pathophysiology. There is no known effective way to prevent scar formation in TED patients, or to reverse scarring once it occurs. In this study, we show that the proton pump inhibitors (PPIs), esomeprazole and lansoprazole, can prevent transforming growth factor beta (TGFβ)-mediated differentiation of TED orbital fibroblasts to myofibroblasts, a critical step in scar formation. Both PPIs prevent TGFβ-induced increases in alpha-smooth muscle actin (αSMA), calponin, and collagen production and reduce TED orbital fibroblast cell proliferation and migration. Esomeprazole and lansoprazole exert these effects through an aryl hydrocarbon receptor (AHR)-dependent pathway that includes reducing β-catenin/Wnt signaling. We conclude that PPIs are potentially useful therapies for preventing or treating TED by reducing the myofibroblast accumulation that occurs in the disease.

    Topics: Actins; Calcium-Binding Proteins; Calponins; Cell Differentiation; Cells, Cultured; Cicatrix; Collagen; Esomeprazole; Fibroblasts; Graves Ophthalmopathy; HEK293 Cells; Humans; Lansoprazole; Microfilament Proteins; Myofibroblasts; Proton Pump Inhibitors; Receptors, Aryl Hydrocarbon; Transforming Growth Factor beta; Wnt Signaling Pathway

2019
Macrophages promote a profibrotic phenotype in orbital fibroblasts through increased hyaluronic acid production and cell contractility.
    Scientific reports, 2019, 07-03, Volume: 9, Issue:1

    Graves' orbitopathy (GO) is an autoimmune inflammatory disease affecting the orbit. Orbital fibroblasts are a key component in GO pathogenesis, which includes inflammation, adipogenesis, hyaluronic acid (HA) secretion, and fibrosis. Macrophages are thought to participate in the immunological stage of GO, but whether they can directly affect the fibroblasts phenotype and modulate disease progression is unknown. We previously showed that GO adipogenic and fibrotic phenotypes could be modelled in a pseudo-physiological 3D environment in vitro. Here, we introduced macrophages in this 3D culture model to investigate role for macrophages in modulating adipogenesis, HA production, and contractility in orbital fibroblasts. Macrophages had a minimal effect on lipid droplet formation in fibroblasts, but significantly increased HA production and cell contractility, suggesting that they may promote the fibrotic phenotype. This effect was found to be mediated at least in part through phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation and linked to an increase in actin polymerization and protrusive activity in fibroblasts. Overall our work shows for the first time a direct role for macrophages in modulating the fibroblasts' phenotype in GO, supporting a role for macrophages in the progression of the fibrotic phenotype through induction of HA production and stimulation of the contractile phenotype in orbital fibroblasts.

    Topics: Actins; Cell Communication; Cells, Cultured; Disease Susceptibility; Fibroblasts; Fibrosis; Graves Ophthalmopathy; Humans; Hyaluronic Acid; Lipid Metabolism; Macrophages; Orbit; Phosphatidylinositol 3-Kinases; Protein Multimerization; Signal Transduction; Transforming Growth Factor beta

2019
Role of microRNA-146a in regulation of fibrosis in orbital fibroblasts from patients with Graves' orbitopathy.
    The British journal of ophthalmology, 2018, Volume: 102, Issue:3

    To examine the role of microRNA-146a (miR-146a) in the regulation of fibrosis in an in vitro model of Graves' orbitopathy (GO).. Orbital fat/connective tissues were harvested from patients with GO and non-GO for primary orbital fibroblast cultures. The effects of transforming growth factor-β (TGF-β), a potent cytokine that promotes fibrosis, on miR-146a expression were analysed in GO and non-GO orbital fibroblasts using quantitative real-time PCR. The effects of overexpressed miR-146a on TGF-β-induced fibrotic markers were examined in GO orbital fibroblasts by western blot analysis. Expression ofSma and Mad related family (Smad) 4/tumour necrosis factor receptor-associated factor 6 (TRAF6) after transfection of miR-146a mimics or inhibitors were examined.. TGF-β induced an increase in miR-146a expression in orbital fibroblasts from patients with GO in a time-dependent and concentration-dependent manner. miR-146a mimics further decreased the production of TGF-β-induced fibronectin, collagen Iα and α-smooth muscle actin protein. The Smad4 and TRAF6 protein levels were significantly decreased by miR-146a mimics, compared with control mimics, and significantly increased on inhibition of miR-146a production compared with a control.. miR-146a plays a role as a negative regulator in the production of TGF-β-induced fibrotic markers. Thus, miR-146a may be involved in the regulation of fibrosis in orbital fibroblasts from patients with GO.

    Topics: Actins; Blotting, Western; Cells, Cultured; Collagen Type I; Dose-Response Relationship, Drug; Fibroblasts; Fibronectins; Fibrosis; Gene Expression Regulation; Graves Ophthalmopathy; Humans; Intracellular Signaling Peptides and Proteins; MicroRNAs; Orbit; Phosphorylation; Real-Time Polymerase Chain Reaction; Smad4 Protein; Time Factors; TNF Receptor-Associated Factor 6; Transfection; Transforming Growth Factor beta

2018
Celecoxib and Pioglitazone as Potential Therapeutics for Regulating TGF-β-Induced Hyaluronan in Dysthyroid Myopathy.
    Investigative ophthalmology & visual science, 2016, Apr-01, Volume: 57, Issue:4

    To investigate the role of extraocular muscles (EOM) myoblasts in Graves ophthalmopathy (GO) pathology and the effect of a cyclooxygenase (COX)-2 inhibitor and a peroxisome proliferator-activated receptor (PPAR)-γ agonist in its treatment.. Myoblasts were isolated and cultured from EOM of 10 patients with GO and 4 without (non-GO). The cultured myoblasts were treated with IFN-γ, insulin-like growth factor (IGF)-1, IL-1β, and TNF-α, and the effect on PPAR-γ, COX-2, TGF-β, and thyroid stimulating hormone receptor (TSH-R) expressions were assessed using real-time (RT)-PCR, ELISA, and Western blot. The effect of a COX-2 inhibitor and a PPAR-γ agonist on the expression of TGF-β, hyaluronan synthases (HAS)-1, -2, and -3, and hyaluronan (HA) were further evaluated.. Real-time PCR showed significant upregulation in PPAR-γ, COX-2, TGF-β, and TSH-R mRNA expression in GO myoblasts when treated with TNF-α but not in the non-GO. While IFN-γ and IGF-1 had no significant effect, IL-1β did upregulate COX-2 expression. These results were further confirmed by ELISA and Western blotting. Tumor necrosis factor α-induced TGF-β in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2. The cyclooxygenase 2 inhibitor and PPAR-γ agonist substantially diminished this TNF-α-induced TGF-β, HA, and HAS3 expression.. These results demonstrate the role of EOM myoblasts in the pathogenesis of GO. The cyclooxygenase 2 inhibitor and PPAR-γ agonist in this study are potential treatments for GO due to their ability to suppress TNF-α-induced TGF-β, HAS, and HA upregulation.

    Topics: Adult; Blotting, Western; Case-Control Studies; Celecoxib; Cells, Cultured; Cyclooxygenase 2 Inhibitors; Enzyme-Linked Immunosorbent Assay; Female; Graves Ophthalmopathy; Humans; Hyaluronic Acid; Male; Middle Aged; Myoblasts; Oculomotor Muscles; Pioglitazone; PPAR gamma; Real-Time Polymerase Chain Reaction; Thiazolidinediones; Transforming Growth Factor beta

2016
The protective effect of antioxidants on orbital fibroblasts from patients with Graves' ophthalmopathy in response to oxidative stress.
    Molecular vision, 2013, Volume: 19

    To investigate the biphasic effects of hydrogen peroxide (H2O2) on the orbital fibroblasts of patients with Graves' ophthalmopathy (GO) and the relation to antioxidants and proinflammatory cytokines.. Proliferation of cultured orbital fibroblasts from patients with GO and normal controls was evaluated in response to various concentrations of H2O2. The effect of low concentrations of H2O2 (6.25 μM) on the cellular proliferation and induction of intracellular proinflammatory cytokines, and reactive oxygen species of orbital fibroblasts were assessed. Protective effects of N-acetylcysteine and vitamin C on GO fibroblasts in response to 6.25 μM H2O2 stimulation were also investigated.. When the GO fibroblasts were exposed to H2O2 at a concentration of 50 μM or above, significant cytotoxicity was observed. In contrast, lower concentrations of H2O2 (3.125-25 μM) increased the survival of GO fibroblasts with the peak cellular proliferation at 6.25 μM H2O2. However, this biphasic effect of H2O2 on the viability of orbital fibroblasts was not found in normal controls. In addition, 6.25 μM H2O2 led to significant elevation of the levels of transforming growth factor, beta 1, interleukin-1β, and superoxide anion in GO fibroblasts, but no significant change in the normal controls. Pretreatment with N-acetylcysteine or vitamin C reversed the enhanced proliferation capacity and the induction of transforming growth factor, beta 1, interleukin-1β and superoxide anion of GO fibroblasts in response to 6.25 μM H2O2.. These findings revealed the biphasic effect of H2O2 on cellular proliferation of GO orbital fibroblasts. Importantly, a low level of H2O2 can stimulate proliferation of GO orbital fibroblasts and induce the production of proinflammatory cytokines, which can be inhibited by pretreatment with antioxidants. This provides a theoretical basis for the rational use of antioxidant in treating GO at an early stage.

    Topics: Acetylcysteine; Adult; Antioxidants; Ascorbic Acid; Cell Proliferation; Cell Survival; Female; Fibroblasts; Graves Ophthalmopathy; Humans; Hydrogen Peroxide; Interleukin-1beta; Intracellular Space; Male; Orbit; Oxidative Stress; Protective Agents; Transforming Growth Factor beta

2013
Orbital fibroblasts from thyroid eye disease patients differ in proliferative and adipogenic responses depending on disease subtype.
    Investigative ophthalmology & visual science, 2013, Nov-08, Volume: 54, Issue:12

    Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation.. Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ(-12,14)-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [(3)H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied.. Type II OFs incorporated 1.7-fold more [(3)H]thymidine than type I OFs (P < 0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P < 0.05) and 12.6-fold more lipid than non-TED OFs (P < 0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs.. We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis.

    Topics: Adipogenesis; Analysis of Variance; Cell Differentiation; Cell Proliferation; Cyclooxygenase Inhibitors; Fibroblasts; Flow Cytometry; Graves Ophthalmopathy; Humans; Orbit; Prostaglandin D2; Transforming Growth Factor beta

2013
Genetic susceptibility to Graves' ophthalmopathy: The role of polymorphisms in anti-inflammatory cytokine genes.
    Ophthalmic genetics, 2010, Volume: 31, Issue:4

    Various polymorphisms occur in cytokine genes involved in inflammatory processes in Graves' ophthalmopathy (GO). Anti-inflammatory cytokines such as transforming growth factor- β (TGF-β), interleukin-10 (IL-10) and interleukin-4 (IL-4) are among those believed to be involved in the disease process. In this study, we investigated the association between 8 polymorphisms within the mentioned cytokines and GO.. The following polymorphisms were studied in 50 patients with GO, 57 Graves' patients without GO and 140 healthy individuals using polymerase chain reaction with sequence-specific primers: TGF-β (+869C/T, +915G/C), IL-10 (-1082A/G, -819C/T, -592C/A) and IL-4 (-1098T/G, -590T/C, -33C/T). A corrected p value less than 0.05 was considered statistically significant.. The TGF-β +915C allele (Odds Ratio [OR] = 2.20) and CC genotype (OR = 7.50) as well as +869C allele (OR = 2.21) showed significant correlations with GO. Regarding IL-4 polymorphisms, the -1098G allele (OR = 2.09) and GG genotype (OR = 7.49), and the -33T allele (OR = 2.05) and TT genotype (OR = 4.00) were significantly associated with GO. The IL-10 -819TT genotype (OR = 5.00) was significantly correlated with GO.. This is the first study to show that polymorphisms in anti-inflammatory cytokine genes are associated with susceptibility to GO.

    Topics: Adult; Case-Control Studies; Cytokines; DNA Primers; Female; Genetic Predisposition to Disease; Graves Ophthalmopathy; Humans; Interleukin-10; Interleukin-4; Male; Polymerase Chain Reaction; Polymorphism, Genetic; Transforming Growth Factor beta

2010
Potential benefit of angiotensin converting enzyme inhibitors for hindering progression of Graves' ophthalmopathy.
    Medical hypotheses, 2008, Volume: 70, Issue:4

    Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Cytokines; Disease Progression; Graves Ophthalmopathy; Humans; Hyaluronic Acid; Models, Biological; Models, Theoretical; Transforming Growth Factor beta; Treatment Outcome

2008