IL1 and megakaryocytes in obesity (WP2865)
Homo sapiens
Schematic of the effects of interleukin (IL)1-beta/IL1R1 on megakaryocyte and platelet function. A high fat diet will cause megakaryocytes to produce platelets with an increase in both inflammatory and thrombotic genes. IL1-beta in circulation as a result of increased body weight will bind IL1R1 on megakaryocytes. This interaction leads to the activation of the nuclear factor (NF)kB, PI3K/Akt, and mitogen activated protein kinase (MAPK) (ERK and p38) pathways. As a result, there is an increase in megakarycoyte maturation, including increased adhesion, increases in ploidy, and increases in mRNA production of inflammatory and thrombotic genes. IL1-beta can also bind IL1R1 on platelets and either enhance aggregation induced by agonists or promote adhesion and heterotypic aggregate formation. Some of the data used to create the pathway was generated in mouse (noted in pathway), however the pathway represents human homologs of those genes. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2865 CPTAC Assay Portal]
Authors
Kristina Hanspers , Marianthi Kalafati , Jonathan Mélius , Andika Tan , Susan Coort , and Egon WillighagenActivity
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Cited In
- Transcriptomic changes in peripheral blood mononuclear cells with weight loss: systematic literature review and primary data synthesis (2021).
- Identification of biomarkers and pathways for the SARS-CoV-2 infections that make complexities in pulmonary arterial hypertension patients (2021).
- Network-based identification genetic effect of SARS-CoV-2 infections to Idiopathic pulmonary fibrosis (IPF) patients (2020).
- 24h-gene variation effect of combined bevacizumab/erlotinib in advanced non-squamous non-small cell lung cancer using exon array blood profiling (2017).
- In silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions (2023).
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Organisms
Homo sapiensCommunities
Diseases ExRNAAnnotations
Disease Ontology
overnutrition obesityPathway Ontology
obesity pathway interleukin-1 signaling pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| IL1R1 | GeneProduct | ncbigene:3554 | |
| PAR1 | GeneProduct | ncbigene:2149 | |
| ICAM1 | GeneProduct | ncbigene:3383 | |
| IL1B | GeneProduct | ncbigene:3553 | |
| TIMP2 | GeneProduct | ncbigene:7077 | |
| SELENBP1 | GeneProduct | ncbigene:8991 | |
| MMP9 | GeneProduct | ncbigene:4318 | |
| PLA2G7 | GeneProduct | ncbigene:7941 | |
| IRAK1 | GeneProduct | ncbigene:3654 | |
| TLR1 | GeneProduct | ncbigene:7096 | |
| IL18 | GeneProduct | ncbigene:3606 | |
| MYD88 | GeneProduct | ncbigene:4615 | |
| TIMP1 | GeneProduct | ncbigene:7076 | |
| CCR3 | GeneProduct | ncbigene:1232 | |
| PIK3CA | GeneProduct | ncbigene:5290 | |
| NLRP3 | GeneProduct | ncbigene:114548 | |
| FCER1A | GeneProduct | ncbigene:2205 | |
| Thrombin | GeneProduct | ncbigene:2147 | |
| IFNG | GeneProduct | ncbigene:3458 | |
| S100A9 | GeneProduct | ncbigene:6280 | |
| HBEGF | GeneProduct | ncbigene:1839 | |
| CCL2 | GeneProduct | ncbigene:6347 | |
| TLR2 | GeneProduct | ncbigene:7097 | |
| NFKB1 | GeneProduct | ncbigene:4790 |
References
- Interleukin 1 receptor 1 and interleukin 1β regulate megakaryocyte maturation, platelet activation, and transcript profile during inflammation in mice and humans. Beaulieu LM, Lin E, Mick E, Koupenova M, Weinberg EO, Kramer CD, et al. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):552–64. PubMed Europe PMC Scholia