A Comprehensive Metabolic Modeling of Thyroid Pathway in Relation to Thyroid Pathophysiology and Therapeutics

Gupta, Manish Kumar; Singh, Dev Bukhsh; Shukla, Rohit; Misra, Krishna

doi:10.1089/omi.2013.0007

Cited by 13 publications

(4 citation statements)

References 73 publications

(60 reference statements)

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“…The transcription factors members of the AP-1 family are involved in the regulation of thyroid growth and thyroid genes expression [34,35,36,37]. Further, quercetin has an opposite role in AP-1 activation, since it increases AP-1 activity in some in vitro models [38,39], whereas it decreases it in other models [40,41].…”

Section: Resultsmentioning

confidence: 99%

“…The present study particularly focused on AP-1 activation for two reasons: First, the AP-1 family of transcription factors is involved in the regulation of thyroid growth and thyroid genes expression [21,34,35,36,37], second, quercetin can increase AP-1 activity in several cell types [38,39,46,47], although no data were available about thyroid cells.…”

Section: Discussionmentioning

confidence: 99%

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The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells

Giuliani

2019

Antioxidants

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Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal activity of the reporter vector. Therefore, the action of quercetin has been evaluated on the basal activity of several reporter vectors: The PGL3 basic, promoter and control vectors from Promega, and a pSV-based chloramphenicol acetyltransferase (CAT) reporter vector. In the Fisher Rat Thyroid cell Line FRTL-5 thyroid cells transiently transfected, quercetin 10 μM increased the basal activity of all the reporter vectors evaluated, although the degree of the effect was significantly different among them. The analysis of the difference among the regulatory regions of these vectors identified the activator protein 1 (AP-1) binding site as one of the potential sites involved in the quercetin effect. Electromobility shift assay experiments showed that the treatment with quercetin induced the binding of a protein complex to an oligonucleotide containing the AP-1 consensus binding site. This is the first study showing an effect of quercetin on AP-1 activity in thyroid cells. Further studies are in progress to understand the role of AP-1 activation in the effects of quercetin on thyroid function.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells

Giuliani

2019

Antioxidants

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“…However, the example of breast cancer studies clearly indicates the need for combining the metabolomics information with other systems biology datasets to provide the holistic view of the processes ongoing in this endocrine malignancy. Such metabolomics network has already been created for thyroid hormone secretion pathway, which helped to identify the potential drug targets essential in treatment of thyroid disorders such as hypo- or hyperthyroidism [ 133 , 134 ]. Along with the technological development of analytical tools (first of all MS- and NMR-based spectral techniques), metabolomics becomes an emerging research approach also in the field of thyroid cancer.…”

Section: Discussionmentioning

confidence: 99%

Application of Metabolomics in Thyroid Cancer Research

Wojakowska

Chekan

Widłak

et al. 2015

International Journal of Endocrinology

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Thyroid cancer is the most common endocrine malignancy with four major types distinguished on the basis of histopathological features: papillary, follicular, medullary, and anaplastic. Classification of thyroid cancer is the primary step in the assessment of prognosis and selection of the treatment. However, in some cases, cytological and histological patterns are inconclusive; hence, classification based on histopathology could be supported by molecular biomarkers, including markers identified with the use of high-throughput “omics” techniques. Beside genomics, transcriptomics, and proteomics, metabolomic approach emerges as the most downstream attitude reflecting phenotypic changes and alterations in pathophysiological states of biological systems. Metabolomics using mass spectrometry and magnetic resonance spectroscopy techniques allows qualitative and quantitative profiling of small molecules present in biological systems. This approach can be applied to reveal metabolic differences between different types of thyroid cancer and to identify new potential candidates for molecular biomarkers. In this review, we consider current results concerning application of metabolomics in the field of thyroid cancer research. Recent studies show that metabolomics can provide significant information about the discrimination between different types of thyroid lesions. In the near future, one could expect a further progress in thyroid cancer metabolomics leading to development of molecular markers and improvement of the tumor types classification and diagnosis.

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“…KEGG, REACTOME, Ingenuity IPA, MetaCore, etc .) have served as an invaluable resource [ 24 , 25 ], facilitating many large-scale pathway modelling studies in recent years [ 26 , 27 ]. However, information about cell-type specific pathways is not commonly available in these online repositories.…”

Section: Discussionmentioning

confidence: 99%

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts

et al. 2015

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The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

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A Comprehensive Metabolic Modeling of Thyroid Pathway in Relation to Thyroid Pathophysiology and Therapeutics

Cited by 13 publications

References 73 publications

The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells

The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells

Application of Metabolomics in Thyroid Cancer Research

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts

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