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RNA-seq for the tissues of GGPPS knockout mice and wild type mice

ABSTRACT: Protein prenylation has multiple important physiological function, but the evidence has been to be explored. Now we found that eicosanoid metabolism homestasis was broken after GGPPS deletion in neonatal vascular smooth muscles through GGPP prenylation.

ORGANISM(S): Mus musculus

PROVIDER: GSE142820 | GEO | 2020/10/03

REPOSITORIES: GEO

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Project description:The aim of the experiment was to study the transcriptome changes occuring after doxycycline treatment of the enriched vascular smooth muscles (eVSM) population.

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Microarray analysis of the Endo and eVSM populations for the A2lox.i8TFs cell line

Project description:The aim of the experiment was to study the transcriptome changes occuring after overexpression of Erg, Fli1, Tal1, Lyl1, Lmo2, Runx1, Cbfb and Gata2 in endothelial (Endo) and enriched vascular smooth muscles (eVSM) populations.

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GGTase-Iβ deletion in Intestinal Epithelial Cells

Project description:Prenylation is a post-translational modification of proteins consisting on the attachment of a lipid residue (isoprenoid). GGTase-I is one of the prenyltransferases catalyzing prenylation. Using mice with an inducible intestinal epihtelial cell specific deletion of GGTase-Iβ we analyzed the impact of geranylgeranylation within intestinal epithelium.

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Expression data from mouse neonatal hindlimb muscles

Project description:During neonatal development, skeletal muscle grows dramatically by myonuclei accretion to existing fibers and hypertophic growth of fibers with protein synthesis. To understand molecular mechanism underlying neonatal muscle growth, we used microarray to profile the global program of gene expressions especially involved in myoblast fusion, migration, and muscle fiber growth by itself. Mouse hindlimb muscles at postnatal day (P) 2, 7, and 14 were isolated and used for RNA extraction and hybridyzation on microarrays. We used three biological replicates for each time point.

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Role of mevalonate pathway intermediates in anticancer effect of statins

Project description:Simvastatin has been widely used for treatment of hypercholesterolemia due to its ability to inhibit HMG-CoA reductase, the rate limiting enzyme of de novo cholesterol synthesis via mevalonate pathway. Its inhibitory action causes also depletion of pathway intermediates, farnesyl pyrophosphate (FPP) and geranyl-geranyl pyrophosphate (GGPP), which are inevitable for proper targeting of small GTPases (e.g. Ras proteins) to their site of action. We profiled by array the gene expression of MIA PaCa-2 cells treated with simvastatin, FPP, GGPP and their combinations. The inhibitory effect of statins on GFP-K-Ras protein trafficking were partially prevented by addition of the mevalonate pathway intermediates. We conclude that the anticancer effect of simvastatin is to a large extent mediated through isoprenoid intermediates of the mevalonate pathway.

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Cholesterol metabolism drives regulatory B cell IL-10 through geranylgeranyl pyrophosphate

Project description:Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) was required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications controlled signaling through PI3Kd-AKT-GSK3, which in turn promoted BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome, termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cells from MKD patients induced poor IL-10 responses and were functionally impaired. Moreover, metabolic supplementation with GGPP was able to reverse this defect. Collectively, our data define cholesterol metabolism as an integral metabolic pathway for the optimal functioning of human IL-10 producing regulatory B cells.

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Project description:Human aortic smooth muscles are quiesced for 24 hours followed by treatment with thrombin for 2 hours and 8 hours in presence or absence of cyclosporin A (10 micromolar) to analyze the effect of thrombin on expression pattern of various genes in presence of cyclosporin A.

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