Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Differential gene expression to VEGF in aorta from wild-type and C42S PKARI knock-in mice

ABSTRACT: Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked-to tumorigenesis, rheumatoid arthritis and heart disease. Here we show pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RI? subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as 'redox-dead' Cys17Ser RI? knock-in mice fully resistant to PKA disulphide-activation have deficient angiogenesis in models of hind limb ischaemia and tumour-implant growth. Disulphide-activation of PKA represents a new therapeutic target in diseases with aberrant angiogenesis. The aim of this study was to identify unique differences in gene expression that may account for decreased angiogenesis in C42S PKARI knock-in mice compared with their littermate wild-types observed in cell and whole animal studies Freshly isolated mouse aortic vessels from 3 C42S PKARI knock-in or 3 littermate wild-types were used in this study. Each vessel was divided in two rings and either left untreated or treated with VEGF.

ORGANISM(S): Mus musculus

SUBMITTER: Matthew Arno

PROVIDER: E-GEOD-70216 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The oocyteâs capacity to complete maturation, to succeed fertilization and to reach the blastocyst stage is what defines the oocyteâs competence. The oocyte acquires this competence working closely with somatic cells of the follicle. Cumulus and granulosa cells provided support for the oocyteâs development and conversely the oocyte influence follicular cell growth and differentiation. Existing studies support the idea that follicular-stimulated hormone and luteinizing hormone play an essential role in oocyte competence acquisition through protein kinase A (PKA) and protein kinase C (PKC) signalling in granulosa cells. Therefore, human-like granulosa cells (KGN) were treated with forskolin 10 Î¼M and phorbol 12-myristate 13-acetate 0.1 Î¼M for 24 hours in order to process a transcriptomic analysis of differentially express genes between treatment. Over 2000 genes were founded to be differentially express at cut-off fold change of 1.5 and a p-value of 0.05. Five major upstreams, EGF, TGFB1, VEGF, FGF2 and HGF were founded to play an important role in competence acquisition thought PKA and PKC signalling. Differentially expressed targeted genes of both signalling pathways were classified in seven major ovarian functions such as PTGS2, IL8 and IL6 in inflammation, STAR, CYP11A1, CYP19A1 in steroidogenesis, VEGFC, VEGFA, CXCR4 in angiogenesis, AREG, EGFR, SPRY2 in differentiation, BAX, BCL2L12, CASP1 in apoptosis, CCND1, CCNB1, CCNB2 in division and MMP1, MMP9, TIMP1 in ovulation. Taken together, the results of this study suggest that PKA and PKC signalling potentiate their effects in some functions such as inflammation and apoptosis while some others are more specific to one or the other protein kinase like differentiation, ovulation and angiogenesis that are thought to be more PKC-dependent in human granulosa cells. 8 samples were analysed, 4 controls compared to 4 Phorbol 12-myristate 13-acetate treatments (total of 4 replicates).

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Differential gene expression to VEGF in aorta from wild-type and C42S PKARI knock-in mice

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