title: A comprehensive metabolic modeling of thyroid pathway in relation to thyroid pathophysiology and therapeutics.
abstract: The thyroid pathway represents a complex interaction of different glands for thyroid hormone synthesis. Thyrotropin releasing hormone is synthesized in the hypothalamus and regulates thyrotropin stimulating hormone gene expression in the pituitary gland. In order to understand the complexity of the thyroid pathways, and using experimental data retrieved from the biomedical literature (e.g., NCBI, HuGE Navigator, Protein Data Bank, and KEGG), we constructed a metabolic map of the thyroid hormone pathway at a molecular level and analyzed it topologically. A total of five hub nodes were predicted in regards to the transcription thyroid receptor (TR), cAMP response element-binding protein (CREB), signal transducer and activator of transcription 3 (STAT 3), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), and activator protein 1 (AP-1) as being potentially important in study of thyroid disorders and as novel putative therapeutic drug targets. Notably, the thyroid receptor is a highly connected hub node and currently used as a therapeutic target in hypothyroidism. Our analysis represents the first comprehensive description of the thyroid pathway, which pertains to understanding the function of the protein and gene interaction networks. The findings from this study are therefore informative for pathophysiology and rational therapeutics of thyroid disorders.
authors.affiliation: 1 Department of Bioinformatics, University Institute of Engineering and Technology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India .
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Gupta
authors.forename: Dev Bukhsh
authors.initials: DB
authors.lastname: Singh
authors.forename: Rohit
authors.initials: R
authors.lastname: Shukla
authors.forename: Krishna
authors.initials: K
authors.lastname: Misra
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D030562:Databases, Protein; D005786:Gene Expression Regulation; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D025941:Protein Interaction Mapping; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D011988:Receptors, Thyroid Hormone; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018808:Transcription Factor AP-1; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin