Expression Profiling of Nme7 Interactome in Experimental Models of Metabolic Syndrome
| Autor: | Josef Vcelak, Elena Školníková, Ondřej Šeda, Běla Bendlová, Lucie Šedová, M Hodúlová |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Physiology Biology Interactome Transcriptome 03 medical and health sciences Species Specificity Rats Inbred SHR Ciliogenesis Gene expression Genetic model Animals Gene Regulatory Networks Gene Metabolic Syndrome Genetics Gene Expression Profiling Cilium General Medicine Lipid Metabolism Rats Gene expression profiling Disease Models Animal 030104 developmental biology Nucleoside-Diphosphate Kinase |
| Zdroj: | Physiological Research. :S543-S550 |
| ISSN: | 1802-9973 0862-8408 |
| DOI: | 10.33549/physiolres.934021 |
| Popis: | Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7) is an acknowledged member of ciliome and is involved in the biogenesis or function of cilia. As obesity and diabetes are common in several ciliopathies, we aimed to analyze changes of gene expression within Nme7 interactome in genetically designed rat models of metabolic syndrome. We assessed the liver transcriptome by Affymetrix microarrays in adult males of 14 PXO recombinant inbred rat strains and their two progenitor strains, SHR-Lx and BXH2. In the strains with the lowest expression of Nme7, we have identified significant enrichment of transcripts belonging to Nme7 interactome. In the subsequent network analysis, we have identified three major upstream regulators – Hnf4a, Ppara and Nr1h4 and liver steatosis (p=0.0001) and liver necrosis/cell death (apoptosis of liver cells, p=0.0003) among the most enriched Tox categories. The mechanistic network reaching the top score showed substantial overlap with Assembly of non-motile cilium and Glucose metabolism disorder gene lists. In summary, we show in a genetic model of metabolic syndrome that rat strains with the lowest expression of Nme7 present gene expression shifts of Nme7 interactome that are perturbing networks relevant for carbohydrate and lipid metabolism as well as ciliogenesis. |
| Databáze: | OpenAIRE |
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