Epigenome analysis of adipose/connective tissue from thyroid-associated ophthalmopathy
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PROVIDER: PRJNA732301 | ENA |
REPOSITORIES: ENA
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Project description:Our study aimed to investigate the differentially expressed lncRNA and circRNAs and their potential roles in orbital adipose/connective tissue from patients with thyroid-associated ophthalmopathy (TAO).
2023-01-16 | GSE143789 | GEO
Project description:Using Illumina Infinium MethylationEPIC 850K BeadChip, the genome-wide DNA methylation difference between adipose/connective tissue from TAO patients and normal subjects were compared
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Project description:lncRNA and circular RNAs in orbital adipose/connective tissue from patients with thyroid-associated ophthalmopathy
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Project description:Thyroid-associated ophthalmopathy (TAO) is a complex eye and orbital disorder that is uniquely linked to Graves’ hyperthyroidism (GH). A popular explanation for the development of orbital inflammation in these patients is autoimmunity against the TSH-receptor expressed in orbital preadipocytes. However, this has not been proven and alternative hypotheses should be entertained. We have shown recently that antibodies against highly purified rabbit skeletal muscle calsequestrin are sensitive and specific markers of eye muscle inflammation in patients with thyroid autoimmunity. Keywords: disease state comparison In the study presented here, RNA from thyroid tissue of hyperthyroid patients with (n=10) and without (n=8) symptoms of ophthalmopathy was compared across 20,589 genes.
2007-10-16 | E-GEOD-9340 | biostudies-arrayexpress
Project description:We measured the expression level of tRFs and mRNAs in thyroid-associated ophthalmopathy patients through high-throughput sequencing technology and verified the expression by quantitative real-time PCR. Then, the possible biological regulation and potential clinical significance of target genes of differentially expressed tRFs were assessed.
2022-02-27 | GSE186480 | GEO
Project description:Thyroid-associated ophthalmopathy (TAO) is a complex eye and orbital disorder that is uniquely linked to Graves’ hyperthyroidism (GH). A popular explanation for the development of orbital inflammation in these patients is autoimmunity against the TSH-receptor expressed in orbital preadipocytes. However, this has not been proven and alternative hypotheses should be entertained. We have shown recently that antibodies against highly purified rabbit skeletal muscle calsequestrin are sensitive and specific markers of eye muscle inflammation in patients with thyroid autoimmunity. Keywords: disease state comparison
2007-10-16 | GSE9340 | GEO
Project description:We identified the differentially expressed mRNAs and lncRNAs/circRNAs of the case group and the control group through high-throughput sequencing technology, performed a functional enrichment analysis of the differentially expressed genes, and used protein-protein interaction (PPI) analysis to identify the hub genes. A novel ceRNA network was successfully established, and the network components may serve as promising diagnostic biomarkers or therapeutic targets for thyroid-associated ophthalmopathy in the future.
2021-10-15 | GSE185952 | GEO
Project description:Orbital fibrosis is a hallmark of tissue remodeling in thyroid-associated ophthalmopathy (TAO). Previous studies have shown that interleukin (IL)-11 plays a pivotal profibrotic role in various inflammatory and autoimmune diseases. However, the expression pattern of IL-11 in patients with TAO and whether IL-11 is mechanistically linked with pathological fibrosis remains unknown. In this study, we investigated IL-11 levels in the serum and orbital connective tissue of patients with TAO, and evaluated the correlation of these levels with the patient’s clinical activity score. We also evaluated the expression pattern of IL-11Rα in orbital connective tissue. Furthermore, we elucidated the regulatory factors, profibrotic function, and downstream signaling pathways for IL-11 in TAO using in vitro studies. Serum and orbital connective tissues IL-11 levels were increased in patients with TAO, as compared with healthy controls. In addition, both levels were positively correlated with disease activity. Single-cell RNA sequencing of orbital connective tissue indicated that IL-11Rα was dominantly expressed in orbital fibroblasts (OFs). RNA sequencing of paired unstimulated and transforming growth factor (TGF)-β1-stimulated samples demonstrated that upregulation of IL-11 expression defined the dominant transcriptional response. IL-11 signaling was also confirmed to be downstream of TGF-β1 and IL-1β. Therefore, we deduced that IL-11 protein is secreted in an autocrine loop in TAO. We also indicated that IL-11 mediated the profibrotic phenotype switch by detecting the expression of myofibroblast differentiation markers, including α-smooth muscle actin and collagen type I α1, which could be abrogated by an anti-IL-11 neutralizing antibody. Furthermore, we revealed that extracellular regulated protein kinase may be a crucial factor in the pro-fibrotic, translationally specific signaling activity of IL-11. These data demonstrate that IL-11 plays a crucial role in orbital fibroblast phenotype switching and may be a potential therapeutic target candidate for the treatment of TAO.
2022-01-28 | GSE194323 | GEO
Project description:Orbital fibrosis is a hallmark of tissue remodeling in thyroid-associated ophthalmopathy (TAO). Previous studies have shown that interleukin (IL)-11 plays a pivotal profibrotic role in various inflammatory and autoimmune diseases. However, the expression pattern of IL-11 in patients with TAO and whether IL-11 is mechanistically linked with pathological fibrosis remains unknown. In this study, we investigated IL-11 levels in the serum and orbital connective tissue of patients with TAO, and evaluated the correlation of these levels with the patient’s clinical activity score. We also evaluated the expression pattern of IL-11Rα in orbital connective tissue. Furthermore, we elucidated the regulatory factors, profibrotic function, and downstream signaling pathways for IL-11 in TAO using in vitro studies. Serum and orbital connective tissues IL-11 levels were increased in patients with TAO, as compared with healthy controls. In addition, both levels were positively correlated with disease activity. Single-cell RNA sequencing of orbital connective tissue indicated that IL-11Rα was dominantly expressed in orbital fibroblasts (OFs). RNA sequencing of paired unstimulated and transforming growth factor (TGF)-β1-stimulated samples demonstrated that upregulation of IL-11 expression defined the dominant transcriptional response. IL-11 signaling was also confirmed to be downstream of TGF-β1 and IL-1β. Therefore, we deduced that IL-11 protein is secreted in an autocrine loop in TAO. We also indicated that IL-11 mediated the profibrotic phenotype switch by detecting the expression of myofibroblast differentiation markers, including α-smooth muscle actin and collagen type I α1, which could be abrogated by an anti-IL-11 neutralizing antibody. Furthermore, we revealed that extracellular regulated protein kinase may be a crucial factor in the pro-fibrotic, translationally specific signaling activity of IL-11. These data demonstrate that IL-11 plays a crucial role in orbital fibroblast phenotype switching and may be a potential therapeutic target candidate for the treatment of TAO.
2022-01-28 | GSE194322 | GEO
Project description:Thyroid-associated ophthalmopathy is a typical autoimmune disease of orbital tissues. Alternative splicing significantly influences many diseases progression, including cancer, age-related macular degeneration, and multiple sclerosis, by modulating the expression of transcripts. However, its role in thyroid-associated ophthalmopathy is still unclear. In this study, differential expression transcripts and differential alternative splicing genes in orbital adipose/connective tissues of thyroid-associated ophthalmopathy patients were detected using RNA sequencing, Cuffdiff, and replicate multivariate analysis of transcript splicing. Three thousand ninety six differential expression transcripts and 2355 differential alternative splicing genes were screened out, while functional enrichment analysis indicated that differential expression transcript and differential alternative splicing genes were associated with immune modulation, extracellular matrix remodeling, and adipogenesis. The expression of the SORBS1, SEPT2, COL12A1, and VCAN gene transcripts was verified by qRT-PCR. In conclusion, prevalent alternative splicing is involved in the disease development in thyroid-associated ophthalmopathy. More attention should be paid to the mechanism of alternative splicing to explore more potential therapeutic targets in thyroid-associated ophthalmopathy.
| S-EPMC8474985 | biostudies-literature