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Investigation of the possible role of Tie2 pathway and TEK gene in asthma and allergic conjunctivitis

ABSTRACT: Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie2 related pathway on a mouse model of asthma. In stage I, 113 SNPs were screened in the TEK gene of the patients in order to search for associations with asthma and allergic conjunctivitis. The top associated SNPs were selected for association studies on the replication cohorts.

INSTRUMENT(S): -

ORGANISM(S): Homo Sapiens

SUBMITTER: SE-GSI

PROVIDER: PRJEB36264 | EVA | 2020-02-26

REPOSITORIES: EVA

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Project description:Sivakumar2011 - EGF Receptor Signaling Pathway EGFR belongs to the human epidermal receptor (HER) family of receptor tyrosine kinases, which consists of four closely related receptors (EGFR (HER1, erbB1), HER2 (neu, erbB2), HER3 (erbB3), and HER4 (erbB4)) that mediate cellular signaling pathways involved in growth and proliferation in response to the binding of a variety of growth factor ligands. There are currently six known endogenous ligands for EGFR: EGF, transforming growth factor- (TGF-), amphiregulin, betacellulin, heparin-binding EGF (HB-EGF), and epiregulin.Upon ligand binding, the EGFR forms homo- or heterodimeric complexes (usually with HER2), which leads to activation of the receptor tyrosine kinase, via autophosphorylation. References: The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. EGF receptor signaling: putting a new spin on eye development. Epidermal growth factor receptor: a promising target in solid tumours. This model is described in the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. Omics: a Journal of Integrative Biology. 2011; 15(10):729-737 Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs. This model is hosted on BioModels Database and identified by: BIOMD0000000394. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

			Action	DRS
	Affymetrix_1.vcf.gz	Vcf
	Affymetrix_1.vcf.gz.tbi	Vcf
	Genotyping_2.vcf.gz	Vcf
	Genotyping_2.vcf.gz.tbi	Vcf

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Investigation of the possible role of Tie2 pathway and TEK gene in asthma and allergic conjunctivitis

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