scholarly journals Orbit-Infiltrating Mast Cells, Monocytes, and Macrophages Produce PDGF Isoforms that Orchestrate Orbital Fibroblast Activation in Graves' Ophthalmopathy

2012 ◽  
Vol 97 (3) ◽  
pp. E400-E408 ◽  
Author(s):  
L. van Steensel ◽  
D. Paridaens ◽  
M. van Meurs ◽  
P. M. van Hagen ◽  
W. A. van den Bosch ◽  
...  
Keyword(s):  
Mast Cells ◽  
Fibroblast Activation ◽  
Graves Ophthalmopathy ◽  
Monocytes And Macrophages ◽  
Orbital Fibroblast ◽  
Pdgf Isoforms

scholarly journals Comprehensive analysis of competitive endogenous RNA associated with immune infiltration in lung adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjie Chen ◽  
Wen Li ◽  
Zhenkun Liu ◽  
Guangzhi Ma ◽  
Yunfu Deng ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Mast Cells ◽  
Correlation Analysis ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Cerna Network ◽  
Monocytes And Macrophages ◽  
Competitive Endogenous Rna

AbstractTo identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan–Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.

The Orbital Fibroblast: A Key Player and Target for Therapy in Graves’ Ophthalmopathy

Orbit ◽  
2010 ◽  
Vol 29 (4) ◽  
pp. 202-206 ◽  
Author(s):  
Leendert van Steensel ◽  
Willem A. Dik
Keyword(s):  
Graves Ophthalmopathy ◽  
Orbital Fibroblast

scholarly journals Integrative Analysis of Proteomics and DNA Methylation in Orbital Fibroblasts From Graves’ Ophthalmopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Sita Virakul ◽  
Poorichaya Somparn ◽  
Trairak Pisitkun ◽  
Peter J. van der Spek ◽  
Virgil A. S. H. Dalm ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Extracellular Matrix ◽  
Rna Polymerase Ii ◽  
Cellular Proliferation ◽  
Effector Function ◽  
Inactive Disease ◽  
Poor Correlation ◽  
Graves Ophthalmopathy ◽  
Orbital Fibroblast ◽  
Orbital Fibroblasts

BackgroundGraves’ ophthalmopathy (GO) is a frequent extrathyroidal complication of Graves’ hyperthyroidism. Orbital fibroblasts contribute to both orbital tissue inflammation and remodeling in GO, and as such are crucial cellular elements in active GO and inactive GO. However, so far it is largely unknown whether GO disease progression is associated with functional reprogramming of the orbital fibroblast effector function. Therefore, the aim of this study was to compare both the proteome and global DNA methylation patterns between orbital fibroblasts isolated from active GO, inactive GO and healthy controls.MethodsOrbital fibroblasts from inactive GO (n=5), active GO (n=4) and controls (n=5) were cultured and total protein and DNA was isolated. Labelled and fractionated proteins were analyzed with a liquid chromatography tandem-mass spectrometer (LC-MS/MS). Data are available via ProteomeXchange with identifier PXD022257. Furthermore, bisulphite-treated DNA was analyzed for methylation pattern with the Illumina Infinium Human Methylation 450K beadchip. In addition, RNA was isolated from the orbital fibroblasts for real-time quantitative (RQ)-PCR. Network and pathway analyses were performed.ResultsOrbital fibroblasts from active GO displayed overexpression of proteins that are typically involved in inflammation, cellular proliferation, hyaluronan synthesis and adipogenesis, while various proteins associated with extracellular matrix (ECM) biology and fibrotic disease, were typically overexpressed in orbital fibroblasts from inactive GO. Moreover, orbital fibroblasts from active GO displayed hypermethylation of genes that linked to inflammation and hypomethylated genes that linked to adipogenesis and autoimmunity. Further analysis revealed networks that contained molecules to which both hypermethylated and hypomethylated genes were linked, including NF-κB, ERK1/2, Alp, RNA polymerase II, Akt and IFNα. In addition, NF-κB, Akt and IFNα were also identified in networks that were derived from the differentially expressed proteins. Generally, poor correlation between protein expression, DNA methylation and mRNA expression was observed.ConclusionsBoth the proteomics and DNA methylation data support that orbital fibroblasts from active GO are involved in inflammation, adipogenesis, and glycosaminoglycan production, while orbital fibroblasts from inactive disease are more skewed towards an active role in extracellular matrix remodeling. This switch in orbital fibroblast effector function may have therapeutic implications and further studies into the underlying mechanism are thus warranted.

scholarly journals Reciprocal interactions between the gut microbiome and mammary tissue mast cells promote metastatic dissemination of HR+ breast tumors

2021 ◽  
Author(s):  
Tzu-Yu Feng ◽  
Francesca N Azar ◽  
Claire B Rosean ◽  
Mitchell T McGinty ◽  
Audrey M Putelo ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Cells ◽  
Gut Microbiome ◽  
Breast Tumor ◽  
Breast Tumors ◽  
Mammary Tissue ◽  
Phenotypic Change ◽  
Fibroblast Activation ◽  
Tumor Dissemination

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, prior to breast tumor initiation, enhances early dissemination of hormone-receptor positive (HR+) mammary tumor cells. Here, we sought to define mammary tissue mediators of dysbiosis-induced tumor dissemination. We found that commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in the mammary tissue, a phenotypic change that persisted after tumor implantation. Fibroblast activation and tissue remodeling associate with enhanced breast tumor metastasis. We employed pharmacological and adoptive transfer approaches to demonstrate that mammary tissue mast cells from dysbiotic animals enhances dissemination of HR+ tumor cells. Collagen levels in mammary tissues from HR+ breast cancer patients correlated with mast cell abundance, suggesting clinical relevance of mast cell-mediated fibroblast activation. Together, these data demonstrate that a gut-mast cell axis exists that induces fibroblast activation and orchestrates early dissemination of HR+ breast tumors.

scholarly journals CXCL4 triggers monocytes and macrophages to produce PDGF-BB, culminating in fibroblast activation: Implications for systemic sclerosis

2020 ◽  
Vol 111 ◽  
pp. 102444 ◽  
Author(s):  
Maarten van der Kroef ◽  
Tiago Carvalheiro ◽  
Marzia Rossato ◽  
Floor de Wit ◽  
Marta Cossu ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Fibroblast Activation ◽  
Monocytes And Macrophages

Comparison of the Expression of Histidine Decarboxylase and Tryptase in Human Skin Mast Cells, Monocytes and Macrophages

2001 ◽  
Vol 124 (1-3) ◽  
pp. 158-159
Author(s):  
Ruth Schiffer ◽  
Jens M. Baron ◽  
Katja Belke ◽  
Ursula Braam ◽  
Hans F. Merk ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Skin ◽  
Histidine Decarboxylase ◽  
Monocytes And Macrophages

scholarly journals PDGF Enhances Orbital Fibroblast Responses to TSHR Stimulating Autoantibodies in Graves' Ophthalmopathy Patients

2012 ◽  
Vol 97 (6) ◽  
pp. E944-E953 ◽  
Author(s):  
L. van Steensel ◽  
H. Hooijkaas ◽  
D. Paridaens ◽  
W. A. van den Bosch ◽  
R. W. A. M. Kuijpers ◽  
...  
Keyword(s):  
Graves Ophthalmopathy ◽  
Orbital Fibroblast

LncRNA LPAL2/miR-1287-5p/EGFR axis modulates TED derived orbital fibroblast activation through cell adhesion factors

2021 ◽  
Author(s):  
Nuo Wang ◽  
Shi-ying Hou ◽  
Xin Qi ◽  
Mi Deng ◽  
Jia-min Cao ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Akt Signaling ◽  
Thyroid Eye Disease ◽  
Differentially Expressed ◽  
Eye Disease ◽  
Fibroblast Activation ◽  
Orbital Fibroblast ◽  
Orbital Fibroblasts ◽  
Adhesion Factor ◽  
Tgf Β1

Abstract Background and aims The activation of orbital fibroblasts, the prime targets in thyroid eye disease, is central to its underlying pathogenesis. We aimed to investigate the mechanism of thyroid eye disease orbital fibroblast activation from the perspective of non-coding RNA regulation. Methods Immunofluorescence (IF) staining was applied to evaluate the fibrotic changes in target cells. Cell proliferation were evaluated by EDU and colony formation assays. Collagen I concentration was determined by ELISA assay. Human microarray analysis was performed on three thyroid eye disease and 3 healthy control orbital tissue samples. Results Bioinformatics analysis showed that cell adhesion signaling factors were differentially expressed in thyroid eye disease tissues, including I-CAM-1, I-CAM-4, V-CAM, and CD44, which were all upregulated in diseased orbital tissues. LncRNA LPAL2 level was also upregulated in orbital tissues and positively correlated with I-CAM-1 and I-CAM-4 expression. Stimulation of the thyroid eye disease orbital fibroblasts by TGF-β1 significantly increased the expression of I-CAM-1, I-CAM-4, and LPAL2. Knockdown of LPAL2 in orbital fibroblasts inhibited TGF-β1-induced increases in cell adhesion factor levels and orbital fibroblast activation. Microarray profiling was performed on thyroid eye disease and normal orbital tissues to identify differentially expressed miRNAs and miR-1287-5p was remarkably reduced within diseased orbital samples. miR-1287-5p was directly bound to EGFR 3’UTR and LPAL2 and LPAL2 modulated EGFR/AKT signaling through targeting miR-1287-5p. Conclusions The LPAL2/miR-1287-5p axis modulated TGF-β1-induced increases in cell adhesion factor levels and thyroid eye disease orbital fibroblast activation through EGFR/AKT signaling.

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