Liver transcriptome study in lambs
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ABSTRACT:
ORGANISM(S): Ovis aries
PROVIDER: GSE125661 | GEO | 2019/02/05
REPOSITORIES: GEO
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Project description:Feeding animals with either concentrates supplemented with vitamin E or alfalfa grazing has been proven to reduce the oxidative process that occurs in meat products. Indoor-kept lambs were fed a standard concentrate (n=7, C) or concentrate supplemented with vitamin E (n=7, VE) for 30 days before slaughtering all animals at 22–24 kg of live weight. Simultaneously, 7 unweaned lambs grazed in alfalfa paddocks (ALF) with their dams. Global transcriptomic data of longissimus thoracis (LT) muscle and subcutaneous fat (SF) with the Affymetrix® Ovine Gene 1.1 microarray was used. In LT muscle when ALF group was compared with C group, were identified 41 genes differentially expressed. Among these genes 32 were down- regulated and 9 were up- regulated. Meanwhile when VE treatment was compared with C group were identified a total of 29 genes, 26 were down- regulated and 3 genes were up- regulated. In SF when ALF treatment was compared with C, were identified only 4 genes differentially expressed, all of them up-regulated in ALF group. Meanwhile when VE treatment was compared with C group, were identified a total of 330 genes. Among them, 295 genes were up- regulated and 35 were down- regulated. In LT muscle the clusters corresponding to gene expression profiles from treatments ALF, C and VE were clearly separated from each other. In SF, ALF group, overlap with VE and C treatments, however, VE and C clearly were separate in different clusters. These differentially expressed genes were selected for a functional analysis by using DAVID. In LT muscle some of the identified significant biological processes were catabolic and lipid process (down-regulated, except CPT1B) (CPT1B, PLA2G16, SPSB1, LRTOMT, PLCD4, FBXO9, CNBP and CYP27A1) and muscle organ differentiation (down-regulated) (CPT1B, MYOD1, MYLK2 and MSTN) in ALF; whereas intracellular signaling cascade (IGF1R, DEF8, AKAP7 and CISH) was down-regulated. In SF, vitamin E supplementation had an important effect; most of the genes were up-regulated. DAVID analysis showed that biosynthesis lipid pathway was the most represented with 20 genes, such as EBP, MVD, CYP51A1, DHCR7, HMGCS1, LSS and FDFT1 implicated in cholesterol synthesis. Further exploration of the links between these genes and vitamin E will lead to a better understanding of how vitamin E affects the oxidative process that occurs in meat products.
2016-12-12 | GSE63774 | GEO
Project description:Although the role of macrophage colony stimulating factor (M-CSF/CSF-1) in homeostasis and disease processes has been studied extensively in mice, little is known of the impact of this cytokine on differentiated human macrophages. Here we show that, in contrast to its effects on mouse bone marrow-derived macrophages (BMM), CSF-1 did not induce expression of urokinase plasminogen activator mRNA, repress expression of apolipoprotein E mRNA, or prime LPS-induced TNF secretion in human monocyte-derived macrophages (HMDM) from several independent donors. Using expression profiling, we show that CSF-1 dynamically regulated the expression of several genes that encode chemokines and chemokine receptors (e.g. CXCL10/IP-10, CXCL2, CCL7, SDF2L1, CXCR4) in HMDM. CSF-1 also upregulated the expression of several genes encoding enzymes of the cholesterol biosynthetic pathway (HMGCR, MVD, IDI1, FDPS, SQLE, CYP51A1, EBP, NSDHL, DHCR7 and DHCR24), while expression of ABCG1, encoding a cholesterol efflux transporter, was repressed. Although the CSF-1/CSF-1R system has been proposed as a target for the treatment of inflammatory and metastatic disease based on studies in rodents, this is the first systematic analysis of the effects of CSF-1 on mature human macrophages. Our data demonstrates that CSF-1 represents a further link between inflammation and cardiovascular disease, inflammtion and immunity. Keywords: Stimulus response
2008-11-14 | GSE11061 | GEO
Project description:Here, we investigated changes of the VSMC transcriptome by utilizing 3D human vascular organoids organized as a core of VSMCs enclosed by a monolayer of ECs. Unbiased microarray-based analyses indicated that interaction with ECs for 48 hours down-regulates the VSMC expression of genes controlling rate-limiting steps of the cholesterol biosynthesis such as HMGCR, HMGCS1, DHCR24 and DHCR7. Protein analyses revealed a decrease in the abundance of 24-dehydrocholesterol reductase and lower cholesterol levels in VSMCs co-cultured with ECs. On the functional level, the blockade of the DHCR24 activity impaired spreading, migration and proliferation of VSMCs. Collectively, these findings indicate that ECs have the capacity to instruct VSMCs to shut down the expression of DHCR24 thereby limiting their capacity for cholesterol biosynthesis which may support their functional steady state.
2020-12-17 | GSE156274 | GEO
Project description:High-throughput sequencing was performed to analyze gene expression profiles of RBE cells after the the inhibition of SQLE or FDFT1 by lentiviruses-mediated shRNA, or RBE cells treated with lycorine hydrochloride.
2023-08-18 | GSE240746 | GEO
Project description:Background: Salinity is an important abiotic stress that influences the physiological and metabolic activity, reproduction, growth and development of marine fish. It has been suggested that half-smooth tongue sole (Cynoglossus semilaevis), a euryhaline fish species, use a large amount of energy to maintain osmotic pressure balance when exposed to fluctuations in salinity. To delineate the molecular response of C. semilaevis to different levels of salinity, we performed RNA-seq analysis of the liver to identify the genes and molecular and biological processes involved in responding to salinity change. Results: The present study yielded 330.4 million clean reads, of which 83.9% were successfully mapped to the reference genome of C. semilaevis. One hundred twenty-eight differentially expressed genes (DEGs), including 43 up-regulated genes and 85 down-regulated genes, were identified. These DEGs were highly represented in metabolic pathways, steroid biosynthesis, terpenoid backbone biosynthesis, butanoate metabolism, glycerolipid metabolism and the 2-oxocarboxylic acid metabolism pathway. In addition, genes involved in metabolism, osmoregulation and ion transport, signal transduction, immune response and stress response, cytoskeleton remodeling, and apoptosis were affected during acclimation to low salinity. Genes acat2, fdps, hmgcr, hmgcs1, mvk, pmvk, ebp, lss, dhcr7, and dhcr24 were up-regulated and abat, ddc, acy1 were down-regulated in metabolic pathways. Genes aqp10 and slc6a6 were down-regulated in osmoregulation and ion transport. Genes abat, fdps, hmgcs1, mvk, pmvk and dhcr7 were first reported to be associated with salinity adaptation in teleosts. Conclusions: Our results revealed that metabolic pathways, especially lipid metabolism were important for salinity adaptation. The candidate genes identified from this study provide a basis for further studies to investigate the molecular mechanism of salinity adaptation and transcriptional plasticity in marine fish.
2018-04-23 | GSE111312 | GEO
Project description:FDFT1 catalyzes the first reaction in the mevalonate/isoprenoid pathway, we demonstrated that FDFT1 down-regulation by two shRNAs significantly reduced cell migration and invasion in highly invasive lung cancer cell lines in vitro, as well as in lung metastases in vivo. We used microarrays to detail the FDFT1 regulated gene expression underlying invasion-metastasis cascade and identified distinct classes of up-regulated genes during this process. Lung adenocarcinoma cells with FDFT1 overexpression were selected for RNA extraction and hybridization on Affymetrix microarrays.
2012-12-31 | E-GEOD-37868 | biostudies-arrayexpress
Project description:Cholesterol is essential for membrane biogenesis, cell proliferation and differentiation. The role of cholesterol in cancer development and the regulation of cholesterol synthesis are still under active investigation. Here we show that under normal-sterol conditions，p53 directly represses the expression of SQLE, a rate-limiting and the first oxygenation enzyme in cholesterol synthesis，in a SREBP2-independent manner. Through transcriptional downregulation of SQLE, p53 represses cholesterol production in vivo and in vitro, leading to tumor growth suppression. Inhibition of SQLE using small interfering RNA (siRNA) or terbinafine (a SQLE inhibitor) reverses the increased cell proliferation caused by p53 deficiency. Conversely, SQLE overexpression or cholesterol addition promotes cell proliferation, particularly in p53 wild-type cells. More importantly, pharmacological inhibition or shRNA-mediated silencing of SQLE restricts nonalcoholic fatty liver disease (NAFLD) -induced liver tumorigenesis in p53 knockout mice. Therefore, our findings reveal a role for p53 in regulating SQLE and cholesterol biosynthesis, and further demonstrate that downregulation of SQLE is critical for p53-mediated tumor suppression.
2021-07-18 | GSE176112 | GEO
Project description:The forkhead box transcription factor FOXO1 is highly expressed in granulosa cells of growing follicles but is down-regulated by FSH in culture or by LH-induced luteinization in vivo. To analyze the function of FOXO1, we infected rat and mouse granulosa cells with adenoviral vectors expressing two FOXO1 mutants: a gain-of-function mutant FOXOA3 that has two serine residues and one threonine residue mutated to alanines rendering this protein constitutively active and nuclear, and a FOXOA3-mutant DNA-binding domain (mDBD) in which the DBD is mutated. The infected cells were then treated with vehicle or FSH for specific time intervals. Infection of the granulosa cells was highly efficient, caused only minimal apoptosis, and maintained FOXO1 protein at levels of the endogenous protein observed in cells before exposure to FSH. RNA was prepared from control and adenoviral infected cells exposed to vehicle or FSH for 12 and 24 h. Affymetrix microarray and database analyses identified, and real time RT-PCR verified, that genes within the lipid, sterol, and steroidogenic biosynthetic pathways (Hmgcs1, Hmgcr, Mvk, Sqle, Lss, Cyp51, Tm7sf2, Dhcr24 and Star, Cyp11a1, and Cyp19), including two key transcriptional regulators Srebf1 and Srebf2 of cholesterol biosynthesis and steroidogenesis (Nr5a1, Nr5a2), were major targets induced by FSH and suppressed by FOXOA3 and FOXOA3-mDBD in the cultured granulosa cells. By contrast, FOXOA3 and FOXOA3- mDBD induced expression of Cyp27a1 mRNA that encodes an enzyme involved in cholesterol catabolism to oxysterols. The genes up-regulated by FSH in cultured granulosa cells were also induced in granulosa cells of preovulatory follicles and corpora lutea collected from immature mice primed with FSH (equine choriogonadotropin) and LH (human choriogonadotropin), respectively. Conversely, Foxo1 and Cyp27a1 mRNAs were reduced by these same treatments. Collectively, these data provide novel evidence that FOXO1 may play a key role in granulosa cells to modulate lipid and sterol biosynthesis, thereby preventing elevated steroidogenesis during early stages of follicle development. Experiment Overall Design: Immature rat granulosa cells were affected with either control (GFP) or FOXO1 mutant adenovirus (FOXOA3 and FOXOA3-mDBD) for 4 hours. Then the cells were treated with either FSH or vehicle for 24 hours. The gene expression profiles for the four treatment samples (control, control +FSH, FOXOA3 + FSH, FOXOA3-mDBD + FSH) were compared using Rat Genome 230.2 Arrays with one array per sample.
2009-04-25 | E-GEOD-15727 | biostudies-arrayexpress
Project description:Previously, we reported apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL) has potent anti-melanoma activity. Herein, we used DNA microarray and bioinformatics to interrogate gene expression profiles of tumors from apoA-I expressing (A-I Tg+/-) versus apoA-I-null (A-I KO) animals to gain insights into mechanisms of apoA-I tumor protection. Differential expression analyses of 11 distinct tumors per group with > 1.2-fold cut off and a false discovery rate adjusted p< 0.05, identified 176 significant transcripts (71 up- and 105 down-regulated in A-I Tg+/- relative to A-I KO group). Bioinformatic analyses identified the mevalonate and de novo serine/glycine synthesis pathways as potential targets for apoA-I anti-tumor activity. Relative to A-I KO, day-7 B16F10L melanoma tumor homografts from A-I Tg+/- exhibited reduced expression of mevalonate-5-pyrophosphate decarboxylase (MVD), a key enzyme targeted in cancer therapy, as well as squalene epoxidase (Sqle), cytochrome P450, family 51 (Cyp51), hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7), and 24-dehydrocholesterol reductase (Dhcr24) with the latter four serving in the sterol synthesis arm of the mevalonate pathway. Phosphoglycerate dehydrogenase (Phgdh), the first enzyme branching off glycolysis in de novo serine synthesis pathway was the most repressed transcript in tumors from A-I Tg+/-. We validated the experimental approach by correlating gene expression patterns in a mouse model where A-I KO is tumor-permissive relative to A-I Tg+/-, with adverse tumor markers previously identified in human melanoma and found 45% concordance. We propose that apoA-I, a physiological serum protein may target the mevalonate and serine synthesis pathways in melanoma cells, in vivo, thus inhibiting the flux of building blocks for macromolecule synthesis that drive rapid tumor growth.
2020-06-04 | GSE137532 | GEO