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Candidate genes mediated by estrogen-related receptor gamma (ERRγ) in pancreatic β cells

ABSTRACT: Recent studies have established the importance of ERRγ as a required participant for insulin secretion in pancreatic β cells. Key downstream genes of ERRγ remain unclear in the pancreatic β cell. To understand the molecular role of ERRγ and elucidate potential key candidate genes involved in pancreatic β cells, the eukaryotic expression plasmid containing mouse ERRγ was constructed and transfected into NIT-1 pancreatic β cells. Overexpression of ERRγ was confirmed by Q-RT-PCR and western blot. RNA-seq was conducted to get the gene expression profiling between the experimental cells and control cells. Differentially expressed genes (DEGs) were identified and subsequently analyzed by gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. We found that overexpression of ERRγ in pancreatic β cells enables regulation of the expression of certain genes involved in cell apoptosis and mitochondrial function, such as TFPT, Bcl7c, Dap, Thoc6, Ube2d3, ATP5H, MPV17, and NDUFA6. GO analysis revealed that the DEGs were mainly enriched in biological regulation, cell, and binding. KEGG pathway analysis demonstrated that DEGs were significantly enriched in infectious diseases, translation annd signal transduction. This study helps to further understand and reposition the molecular mechanisms of ERRγ in pancreatic β cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE122805 | GEO | 2019/11/30

REPOSITORIES: GEO

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Project description:Purpose: The objective of this study was to evaluate the transcriptomic consequence of chronic exposure to deficient and excessive arginine supply in MIN6 pancreatic beta cells and reveal the molecular mechanisms underlying beta cell function and insulin secretion to arginine administration. Methods: After overnight adhesion, the medium was removed, and the cells were incubated in fresh DMEM medium containing low-, standard- or high-arginine concentration (LA, SA and HA) for 24 h. Following the treatment, RNA was extracted from cells for transcriptome sequencing. Results: Transcriptomics analysis allowed the detection of 23,620 and 22,939 transcripts in the LA and HA samples, among which 7,591 (3,736 up- and 3,855 down-regulated) and 197 (111 up- and 86 down-regulated) genes were expressed differently compared with the SA treatment. One hundred and forty one DEGs were overlapped between LA vs. SA and HA vs. SA comparisons, which were mainly involved in DNA replication, organic hydroxy compound metabolism and cellular response to oxidative stress. GO functional enrichment analysis demonstrated that terms related to proteasomal protein catabolic process, mRNA processing and ATP metabolic process were highly disturbed by LA administration, while DEGs induced by HA were mainly enriched to ammonium ion metabolic process, mRNA export and sterol biosynthetic process. Morever, KEGG pathway analysis revealed that DEGs between LA and SA treatments were mainly functionally classified as involved in protein processing in endoplasmic reticulum and oxidative phosphorylation, while DNA replication, steroid biosynthesis and cell cycle had more counts and reached significant difference levels according to the DEGs triggered by HA. Conclusions: These results suggested that the disturbed carbohydrate, lipid and amino acid metabolisms as well as the decreased cell proliferation, increased apoptosis and elevated oxidative stress contributed to the reduced insulin secretion in beta cells induced by LA or HA administrations.

Project description:Objectives: To analyze the gene expression profile of peripheral blood monocytes in different stages of coronary artery disease (CAD) by transcriptome sequencing, and to explore potential genes and pathway involved in CAD pathogenesis. Methods: According to the screening of coronary angiography and quality control of blood samples, 8 intermediate coronary lesion patients were selected, then 8 patients with acute myocardial infarction and 8 patients with normal coronary angiography were matched by age and gender. Transcriptomics sequencing was conducted for the peripheral blood monocytes of these 24 samples by using Illumina HiSeq high-throughput platform. Then differentially expressed genes (DEGs) were analyzed. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and protein-protein interaction (PPI) network were applied to annotate the potential functions of DEGs. Results: Compared with the normal coronary angiography group, we identified a total of 169 DEGs in the intermediate coronary lesion group, which were significantly enriched in 59 GO terms and 17 KEGG pathways. Compared with the normal coronary angiography group, we found a total of 2028 DEGs, which were significantly enriched in 311 GO terms and 20 KEGG pathways in the acute myocardial infarction group. The cross-comparison between normal versus intermediate coronary lesion group, and normal versus acute myocardial infarction group included 98 differential genes with 65 up regulated and 33 down regulated genes, which were significantly enriched in 46 GO terms and 10 KEGG pathways. During the progression of CAD, there was a significant up-regulated expression of CSF3、IL-1A、CCR7 and IL-18, and down-regulated expression of MAPK14. Besides GO items such as inflammatory response was significantly enriched, KEGG analysis showed the most remarkable enrichments in IL-17 signaling pathway and cytokine-cytokine receptor interactions. Conclusions: Transcriptomics profiles vary in patients with different severity of CAD. CSF3、IL-1A、CCR7、IL-18 and MAPK14, as well as IL-17 signaling pathway and cytokines and cytokine receptor interaction signaling pathway related with inflammatory response might be the potential biomarker and targets for the treatment of coronary artery disease.

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Candidate genes mediated by estrogen-related receptor gamma (ERRγ) in pancreatic β cells

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