scholarly journals TGFβ1, MMPs and cytokines profiles in ocular surface: Possible tear biomarkers for pseudoexfoliation

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249759
Author(s):  
Prity Sahay ◽  
Shweta Reddy ◽  
Birendra Kumar Prusty ◽  
Rahul Modak ◽  
Aparna Rao
Keyword(s):  
Growth Factor ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Gelatin Zymography ◽  
Matrix Metalloproteases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Altered Expression ◽  
Gm Csf ◽  
Tenon’S Capsule ◽  
Tenon's Capsule

Purpose Pseudoexfoliation (PXF) is a unique form of glaucoma characterized by accumulation of exfoliative material in the eyes. Changes in tear profile in disease stages may give us insights into molecular mechanisms involved in causing glaucoma in the eye. Methods All patients were categorized into three main categories; pseudoexfoliation (PXF), pseudoexfoliation glaucoma (PXG) and cataract, which served as control. Cytokines, transforming growth factor β1 (TGFβ1), matrix metalloproteases (MMPs) and fibronectin (FN1) were assessed with multiplex bead assay, enzyme-linked immunosorbent assay (ELISA), gelatin zymography, and immunohistochemistry (IHC) respectively in different ocular tissues such as tears, tenon’s capsule, aqueous humor (AH) and serum samples of patients with PXF stages. Results We found that TGFβ1, MMP-9 and FN1 protein expression were upregulated in tears, tenon’s capsule and AH samples in PXG compared to PXF, though the MMP-9 protein activity was downregulated in PXG compared with control or PXF. We have also found that in PXG tears sample the fold change of TGF-α (Transforming Growth Factor-α), MDC (Macrophage Derived Chemokine), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor) were significantly downregulated and the levels of GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IP-10 (Interferon- γ produced protein-10) were significant upregulated. While in AH; IL-6 (Interleukin-6), IL-8, VEGF, IFN-a2 (Interferon- α2), GRO (Growth regulated alpha protein) levels were found lower and IL1a (Interleukin-1α) level was higher in PXG compared to PXF. And in serum; IFN-a2, Eotaxin, GM-CSF, Fractalkine, IL-10 (Interleukin-10), IL1Ra (Interleukin-1 receptor antagonist), IL-7 (Interleukin-7), IL-8, MIP1β (Macrophage Inflammatory Protein-1β), MCP-1 (Monocyte Chemoattractant Protein-1) levels were significantly upregulated and PDGF-AA (Platelet Derived Growth Factor-AA) level was downregulated in the patients with PXG compared to PXF. Conclusions Altered expression of these molecules in tears may therefore be used as a signal for onset of glaucoma or for identifying eyes at risk of developing glaucoma in PXF.

Effect of Cytokines on Regulation of the Production of Transforming Growth Factor Beta-1 in Cultured Human Tenon's Capsule Fibroblasts

2000 ◽  
Vol 10 (2) ◽  
pp. 110-115 ◽  
Author(s):  
P.O. Denk ◽  
S. Roth-Eichhorn ◽  
A.M. Gressner ◽  
M. Knorr
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Conditioned Media ◽  
Filtering Surgery ◽  
Potent Inducer ◽  
Tenon’S Capsule ◽  
Tenon's Capsule ◽  
Tgf Β1

Purpose Transforming growth factor-β1 (TGF-β1) is thought to play a pivotal role in the regulation of the wound healing process after glaucoma filtering surgery. The aim of the present study was to investigate whether platelet-derived growth factor isoforms (PDGF-AA, PDGF-BB), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), in-terleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) modulate the production of latent and/or active TGF-β1 by cultured human Tenon's capsule fibroblasts (HTF). Methods Human Tenon's capsule fibroblasts were seeded at two different densities (30 cells/mm2 and 150 cells/mm2) and stimulated for five days with PDGF-AA, PDGF-BB, bFGF, EGF, IL-1β and TGF-β1. Control cells were treated with serum-free medium (WM/F12). The concentrations of latent and active TGF-β1 in the medium were determined using an immunoassay before and after activation of TGF-β1 by transient acidification. Results The concentration of latent TGF-β1 in conditioned media from HTF seeded at high density (150 cells/mm2) significantly increased after stimulation with 5 ng/ml TGF-β1 (151.5 ± 41.7 pg/ml) or 10 ng/ml IL-1β (45.7 ± 8.1 pg/ml). The concentration of active TGF-β1 in conditioned media also significantly increased after stimulation of HTF with 5 ng/ml TGF-β1 (48.4 ± 27.5 pg/ml). Conclusions The present results indicate that TGF-β1 is the most potent inducer of its own synthesis in HTF. Activation of an autocrine TGF-β1 loop may play a role in the wound healing response after glaucoma filtering surgery.

scholarly journals OP0268 TREATMENT STATUS AFFECTS HOW PULMONARY BIOMARKERS PREDICT PROGRESSION OF SYSTEMIC SCLEROSIS-RELATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 163.1-163
Author(s):  
E. Volkmann ◽  
D. Tashkin ◽  
M. Leng ◽  
N. LI ◽  
G. Kim ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Transforming Growth Factor ◽  
Selection Process ◽  
Linear Regression Models ◽  
Research Support ◽  
Gm Csf ◽  
Treatment Status

Background:The course of interstitial lung disease (ILD) varies considerably in patients with systemic sclerosis (SSc), and no biomarkers have been found to consistently predict ILD progression in this population. Treatment may affect how a candidate biomarker correlates with improvement/worsening of SSc-ILD. We hypothesized that specific proteins recovered from bronchoalveolar lavage (BAL) would differentially predict progression of SSc-ILD based on whether a patient was receiving ILD therapy.Objectives:(1) To assess the relationship between 68 unique BAL proteins measured in participants of Scleroderma Lung Study (SLS) I1 and changes in radiographic extent of SSc-ILD; (2) To determine if treatment affects whether a specific protein predicts improvement or worsening of SSc-ILD.Methods:Bronchoscopy was performed on 144 of the 158 participants in SLS I (Cyclophosphamide [CYC] vs. placebo) with 103 BAL samples available for analysis. BAL was lyophilized, concentrated 10X and used in a multiplex protein analysis of 68 distinct cytokines, chemokines and growth factors. Quantitative imaging analysis (QIA) was used to calculate the extent of radiographic fibrosis (QLF) in the whole lung using HRCT of the chest at baseline and 12 months. Multivariable linear regression models were created to determine the key BAL proteins associated with change in QLF scores using a backward selection process adjusting for treatment arm and ILD severity. The bootstrap procedure was employed for internal validation.Results:A number of BAL proteins were significantly associated with change in QLF scores at 12 months; however, the directionality of these associations was often based on the presence/absence of treatment. For example, increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, monocyte chemoattractant protein (MCP)-3, chemokine ligand (CCL)-5, transforming growth factor (TGF)-β, hepatocyte growth factor (HGF), stem cell factor (SCF), IL-4, TGF-α, were associated with worse QLF scores in patients who received placebo; whereas, increased levels of these same proteins were associated with improved QLF scores in patients who received CYC (Figure). Increased levels of Fractalkine were associated with worse in QLF scores, and increased levels of IL-7 were associated with improved QLF scores, regardless of treatment arm. In the multivariable model adjusting for treatment arm and baseline severity of ILD, IL-1, MCP-3, surfactant protein C, IL-7, and CCL-5 were independently associated with change in QLF scores.Figure 1.Example of a specific BAL protein (GM-CSF) that predicts worse QLF scores in patients receiving placebo (Group B, Red dotted line) and improved QLF scores in patients receiving CYC (Group A, Blue solid line). Shaded areas represent 95% confidence intervals.Conclusion:Proteins that mediate both inflammation and fibrosis differentially affected progression of SSc-ILD based on treatment status. Higher levels of certain proteins predicted worsening of ILD in patients receiving placebo, but improvement in patients receiving CYC. Measuring these proteins could help to identify patients who: (1) are at risk for ILD progression, and (2) may preferentially benefit from treatment with immunosuppression.References:[1]Tashkin DP, et al. NEJM 2006.Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Donald Tashkin: None declared, Mei Leng: None declared, Ning Li: None declared, Grace Kim: None declared, Jonathan Goldin: None declared, Airi Harui: None declared, Michael Roth Grant/research support from: Genentech/Roche

scholarly journals Analytical Characterization of an Enzyme-Linked Immunosorbent Assay for the Measurement of Transforming Growth Factor β1 in Human Plasma

2018 ◽  
Vol 3 (2) ◽  
pp. 200-212 ◽  
Author(s):  
Brendan M Giles ◽  
Timothy T Underwood ◽  
Karim A Benhadji ◽  
Diana K S Nelson ◽  
Lisa M Grobeck ◽  
...  
Keyword(s):  
Growth Factor ◽  
Human Plasma ◽  
Patient Selection ◽  
Transforming Growth Factor ◽  
Sandwich Elisa ◽  
Transforming Growth Factor Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Tgf Β1 ◽  
Apparently Healthy

Abstract Background The transforming growth factor β (TGF-β)–signaling pathway has emerged as a promising therapeutic target for many disease states including hepatocellular carcinoma (HCC). Because of the pleiotropic effects of this pathway, patient selection and monitoring may be important. TGF-β1 is the most prevalent isoform, and an assay to measure plasma levels of TGF-β1 would provide a rational biomarker to assist with patient selection. Therefore, the objective of this study was to analytically validate a colorimetric ELISA for the quantification of TGF-β1 in human plasma. Methods A colorimetric sandwich ELISA for TGF-β1 was analytically validated per Clinical and Laboratory Standards Institute protocols by assessment of precision, linearity, interfering substances, and stability. A reference range for plasma TGF-β1 was established for apparently healthy individuals and potential applicability was demonstrated in HCC patients. Results Precision was assessed for samples ranging from 633 to 10822 pg/mL, with total variance ranging from 28.4% to 7.2%. The assay was linear across the entire measuring range, and no interference of common blood components or similar molecules was observed. For apparently healthy individuals, the average TGF-β1 level was 1985 ± 1488 pg/mL compared to 4243 ± 2003 pg/mL for HCC patients. Additionally, the TGF-β1 level in plasma samples was demonstrated to be stable across all conditions tested, including multiple freeze–thaw cycles. Conclusions The ELISA described in this report is suitable for the quantification of TGF-β1 in human plasma and for investigational use in an approved clinical study.

Association and prognostic value of serum inflammation markers in patients with leukoplakia and oral cavity cancer

2013 ◽  
Vol 51 (6) ◽  
Author(s):  
Pi-Yueh Chang ◽  
Yung-Bin Kuo ◽  
Tsu-Lan Wu ◽  
Chun-Ta Liao ◽  
Yu-Chen Sun ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Transforming Growth Factor ◽  
Oral Cavity Cancer ◽  
Matrix Metalloproteases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammation Markers ◽  
Roc Curve Analysis ◽  
Discrimination Power ◽  
Amyloid A ◽  
Risk Of Cancer

AbstractOral cavity cancer ranks as the fourth leading cancer in men in Taiwan. The development of a serum biomarker panel for early detection and disease monitoring is, therefore, warranted.Nine inflammation-associated markers were investigated in 46 patients with leukoplakia, 151 patients with untreated oral cavity squamous cell carcinoma (OSCC), and 111 age- and gender-matched healthy controls using enzyme-linked immunosorbent assay. During a subsequent 28-month surveillance of OSCC patients, serum samples were prospectively collected at predetermined intervals following the completion of therapy.Logistic regression analysis showed matrix metalloproteases (MMP)-2, MMP-9, C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and E-selectin having the best discrimination power between groups and significant elevation trends of those five markers were noted from control to OSCC. By combining those five markers, a 0.888 and 0.938 area under curve by ROC curve analysis with 67.4% and 80% overall sensitivity and fixed 90% specificity for leukoplakia and OSCC groups were demonstrated. In the follow-up period, 25 OSCC patients developed recurring or secondary tumors. All examined markers had decreased in relapse-free patients following treatment. However, in patients with relapse, interleukin-6, CRP, and serum amyloid A remained at elevated levels. Statistical analysis showed that patients with CRP ≧2 mg/L and E-selectin ≧85 ng/mL at baseline had highest probability of relapse (odds ratio=3.029, p<0.05).The results indicate that inflammation plays a crucial role in the pathogenesis process of OSCC. By examining the inflammation markers, physicians could potentially identify patients at risk of cancer transformation or relapse.

Altered expression of transforming growth factor-beta in Alzheimer's disease

Neurology ◽  
1995 ◽  
Vol 45 (8) ◽  
pp. 1561-1569 ◽  
Author(s):  
K. C. Flanders ◽  
C. F. Lippa ◽  
T. W. Smith ◽  
D. A. Pollen ◽  
M. B. Sporn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Altered Expression ◽  
Growth Factor Beta

VEGF-C mediates cyclic pressure-induced endothelial cell proliferation

2002 ◽  
Vol 11 (3) ◽  
pp. 245-251 ◽  
Author(s):  
Hainsworth Y. Shin ◽  
Michael L. Smith ◽  
Karen J. Toy ◽  
P. Mickey Williams ◽  
Rena Bizios ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Growth Factor ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Culture Conditions ◽  
Endothelial Cell Proliferation ◽  
Cyclic Pressure ◽  
Cell Functions

Mechanical forces modulate endothelial cell functions through several mechanisms including regulation of gene transcription. In the present study, gene transcription by human umbilical vein endothelial cells (HUVEC) either maintained under control pressure (that is, standard cell culture conditions equivalent to 0.15 mmHg sustained hydrostatic pressure) or exposed to 60/20 mmHg sinusoidal pressures at 1 Hz were compared using Affymetrix GeneChip microarrays to identify cellular/molecular mechanisms associated with endothelial cell responses to cyclic pressure. Cyclic pressure selectively affected transcription of 14 genes that included a set of mechanosensitive proteins involved in hemostasis (tissue plasminogen activator), cell adhesion (integrin-α2), and cell signaling (Rho B, cytosolic phospholipase A2), as well as a unique subset of cyclic pressure-sensitive genes such as vascular endothelial growth factor (VEGF)-C and transforming growth factor (TGF)-β2. The present study also provided first evidence that VEGF-C, the most highly induced gene under 60/20 mmHg, mediated HUVEC proliferation in response to this cyclic pressure. Cyclic pressure is, therefore, a mechanical force that modulates endothelial cell functions (such as proliferation) by activating a specific transcriptional program.

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