Expression profiling of Nme7 interactome in experimental models of metabolic syndrome.

摘要

Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7)is an acknowledged member of ciliome and is involved in thebiogenesis or function of cilia. As obesity and diabetes arecommon in several ciliopathies, we aimed to analyze changes ofgene expression within Nme7 interactome in genetically designedrat models of metabolic syndrome. We assessed the livertranscriptome by Affymetrix microarrays in adult males of 14 PXOrecombinant inbred rat strains and their two progenitor strains,SHR-Lx and BXH2. In the strains with the lowest expression ofNme7, we have identified significant enrichment of transcriptsbelonging to Nme7 interactome. In the subsequent networkanalysis, we have identified three major upstream regulators –Hnf4a , Ppara and Nr1h4 and liver steatosis (p=0.0001) and livernecrosis/cell death (apoptosis of liver cells, p=0.0003) among themost enriched Tox categories. The mechanistic network reachingthe top score showed substantial overlap with Assembly ofnon-motile cilium and Glucose metabolism disorder gene lists. In, we show in a genetic model of metabolic syndromethat rat strains with the lowest expression of Nme7 present geneexpression shifts of Nme7 interactome that are perturbingnetworks relevant for carbohydrate and lipid metabolism as wellas ciliogenesis.