Expression Profiling of Nme7 Interactome in Experimental Models of Metabolic Syndrome

0501110 - ÚMG 2019 RIV CZ eng J - Článek v odborném periodiku
Šedová, Lucie - Školníková, Elena - Hodúlová, Miloslava - Včelák, J. - Šeda, O. - Bendlová, B.
Expression Profiling of Nme7 Interactome in Experimental Models of Metabolic Syndrome.
Physiological Research. Roč. 67, č. 3 (2018), s. 543-550. ISSN 0862-8408. E-ISSN 1802-9973
Grant CEP: GA ČR GA17-13491S
Institucionální podpora: RVO:68378050
Klíčová slova: Metabolic syndrome * Transcriptomics * Recombinant inbred strains * Ciliopathy
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 1.701, rok: 2018

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 Nme7interactome 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.
Trvalý link: http://hdl.handle.net/11104/0293440