scholarly journals Effect of Acute Aldosterone Administration on Gene Expression Profile in the Heart

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3183-3189 ◽  
Author(s):  
Alexander Turchin ◽  
Christine Z. Guo ◽  
Gail K. Adler ◽  
Vincent Ricchiuti ◽  
Isaac S. Kohane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Software Tool ◽  
Differentially Expressed ◽  
Control Group ◽  
Myocardial Inflammation ◽  
Acute Administration ◽  
Mrna Levels ◽  
And Control

Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This paper describes an investigation of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration using oligonucleotide microarrays and compared with those of the control animals who underwent a sham injection. A novel software tool (CAGED) designed for analysis of temporal microarray experiments using a Bayesian approach was used to identify genes differentially expressed between the aldosterone-injected and control group. CAGED analysis identified 12 genes as having significant differences in their temporal profiles between aldosterone-injected and control groups. All of these genes exhibited a decrease in expression level 1–3 h after aldosterone injection followed by a brief rebound and a return to baseline. These findings were validated by quantitative RT-PCR. The differentially expressed genes included phosphatases, regulators of steroid biosynthesis, inactivators of reactive oxygen species, and structural proteins. Several of these genes are known to functionally mediate biochemical phenomena previously observed to be triggered by aldosterone administration, such as phosphorylation of ERK1/2. These results provide the first description of cardiac genetic response to aldosterone and identify several potential mediators of known biochemical sequelae of aldosterone administration in the heart.

scholarly journals Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia

2022 ◽  
Vol 12 ◽  
Author(s):  
Beatrice E. Gee ◽  
Andrea Pearson ◽  
Iris Buchanan-Perry ◽  
Roger P. Simon ◽  
David R. Archer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Control Subjects ◽  
Non Coding Rna ◽  
And Control

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.

scholarly journals Gene Expression Profiles of Papillary Thyroid Microcarcinoma

2017 ◽  
Vol 102 (1-2) ◽  
pp. 39-46 ◽  
Author(s):  
Woo Young Kim ◽  
Jae Bok Lee ◽  
Seung Pil Jung ◽  
Hoon Yub Kim ◽  
Sang Uk Woo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Differentially Expressed Genes ◽  
Expression Profile ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Papillary Thyroid Microcarcinoma ◽  
Papillary Thyroid ◽  
Normal Thyroid ◽  
Thyroid Microcarcinoma

The objective was to identify gene expression profile of papillary thyroid microcarcinoma. To help improve diagnosis of papillary thyroid microcarcinoma, we performed gene expression profiling and compared it to pair normal thyroid tissues. We performed microarray analysis with 6 papillary thyroid microcarcinoma and 6 pair normal thyroid tissues. Differentially expressed genes were selected using paired t test, linear models for microarray data, and significance analysis of microarrays. Real-time quantitative reverse transcription–polymerase chain reaction was used to validate the representative 10 genes (MET, TIMP1, QPCT, PROS1, LRP4, SDC4, CITED1, DPP4, LRRK2, RUNX2). We identified 91 differentially expressed genes (84 upregulated and 7 downregulated) in the gene expression profile and validated 10 genes of the profile. We identified a significant genetic difference between papillary thyroid microcarcinoma and normal tissue by 10 upregulated genes greater than 2-fold (P < 0.05).

scholarly journals What Changed on the Folliculogenesis in the Process of Mouse Ovarian Aging?

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wenlei Ye ◽  
Wei Shen ◽  
Wei Yan ◽  
Su Zhou ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Ovarian Function ◽  
Profile Analysis ◽  
Protein Stabilization ◽  
Differentially Expressed ◽  
Microarray Gene Expression ◽  
Primordial Follicles ◽  
Age Related

There are about 1-2 million follicles presented in the ovary at birth, while only around 1000 primordial follicles are left at menopause. The ovarian function also decreases in parallel with aging. Folliculogenesis is vital for ovarian function, no matter the synthesis of female hormones or ovulation, yet the mechanisms for its changing with increasing age are not fully understood. Early follicle growth up to the large preantral stage is independent of gonadotropins in rodents and relies on intraovarian factors. To further understand the age-related molecular changes in the process of folliculogenesis, we performed microarray gene expression profile analysis using total RNA extracted from young (9 weeks old) and old (32 weeks old) mouse ovarian secondary follicles. The results of our current microarray study revealed that there were 371 (≥2-fold, q-value ≤0.05) genes differentially expressed in which 174 genes were upregulated and 197 genes were downregulated in old mouse ovarian secondary follicles compared to young mouse ovarian secondary follicles. The gene ontology and KEGG pathway analysis of differentially expressed genes uncovered critical biological functions such as immune system process, aging, transcription, DNA replication, DNA repair, protein stabilization, and apoptotic process were affected in the process of aging. The considerable changes in gene expression profile may have an adverse influence on follicle quality and folliculogenesis. Our study provided information on the processes that may contribute to age-related decline in ovarian function.

The Challenge of Using CB-HSCs As Source for Gene Therapy: Lentiviral Vector Transduction, Phenotypic Characterization and Global Gene Expression Profile of Ex-Vivo Expanded CB CD34+ Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5548-5548
Author(s):  
Rosalia Di Stefano ◽  
Elena Baiamonte ◽  
Melania Lo Iacono ◽  
Barbara Spina ◽  
Flavia Contino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Culture Conditions ◽  
Differentially Expressed ◽  
Cd34 Cells

Abstract Introduction: Genetic modification of autologous hematopoietic stem and progenitor cells (HSPC) is a promising clinical intervention to cure inherited monogenic diseases. Successful gene therapy trials have already been conducted using CD34+ cells from bone marrow and from mobilized peripheral blood. In this regard, cord blood (CB) represents an attractive source of HSCs due to its high concentration of high proliferative HSPC and increased susceptibility to be transduced by lentiviral vectors. Unfortunately, the major disadvantage is the limited number of HSC in the CB collection. Consequently, ex-vivo expansion of CB-HSC is desirable to extend clinical applications. Purposes: To investigate the ability of UCB-cd34+ cells to be expanded in serum-free media supplemented with the early acting hematopoietic cytokines SCF,TPO and Flt-3 ligant (STF) and to characterize CD34+ cells subtypes, clonogenic capacity and gene expression profile during expansion. We also wanted to investigate the susceptibility of the expanded cd34+ cells to be transduced by a GFP-lentiviral vector (LV-GFP) Material and Methods: CD34+ immunoselected cells from 10 UCB were grown for 8 days in customized serum-free medium formulated for HSC expansion, supplemented with STF cytokines. Numbers end frequency of CD34+cells and co-expression of the primitive surface antigens (CD38, CD133, CD90) was evaluated during expansion. Colonies developed in methylcellulose were scored for enumeration ad typing. LV-GFP transduction efficiency was evaluated in CD34+ cells cultured for 4 days in expansion medium plus STF and for 24 hrs in X-vivo10 medium with STF±IL-3 cytokines; the last condition slightly expands CD34+ cells (1.3 fold) and are currently used for HSPC-lentivector transduction in gene therapy clinical trials. The transduction efficiency was evaluated by measuring the percentage of GFP+ cells in the bulk and in colonies developed in methylcellulose and the VCN/cell by Q-PCR. Gene expression profiles were analyzed by human whole genome Agilent microarray Technology to detect differentially expressed genes between expanded, ex-vivo medium cultured and un-cultured cells. Results: We found an average of 8 fold-increase CD34+cells at day 4 and of 22 fold- increase at day 8 of culture. The frequency of CD34+ was maintained at day 4 and declined of about 50% at day 8. CD34+/CD38- early progenitors doublet as early as day 4, differences in CD34+/CD133+ and CD34+/CD90+cells were not significant. The number of CFU slightly increased during expansion while the relative frequency of colonies type did not significantly changed. Four days expanded CD34+ cells were transduced more efficiently than those grown in ex-vivo medium even in presence of IL-3 added to the STF cytokine cocktail. Comprehensive gene expression profile analysis highlighted about 4000 genes differentially expressed in CD34+ cells expanded for 4 and for 8 days compared to that of the un-cultured cells. Conversely, the expression profiles analysis did not show any clear separation between different cell culture methods (expansion vs ex-vivo medium). Specifically, the number of differentially expressed genes in common between the different culture conditions compared with the un-cultured cells was statistically significant. Unsurprisingly, the common up-regulated genes were related to the cell cycle. The likeness between the gene expression profiles of the different culture conditions was also validated by the identification of a significantly small number of differentially expressed genes between them. Conclusions: UCB-CD34+ cells can be efficiently expanded and transduced in serum free conditions. The expanded cells exhibited phenotypic marchers typical of early progenitors and developed colonies in number and in type similar to the unmanipulated cells and exhibited whole gene expression profile that is consisted with that of CD34+ cells exposed for the short term culture conditions currently used in gene therapy trial mediated by lentiviral vectors. Results from this study open a window on the future possibility of using homologous UCB-HSC as target for gene correction in patients diagnosed for a genetic disorder in prenatal time. The genetically modified cells would be stored and used for gene therapy in the same individual in pediatric age. This work was funded by the F and P Cutino Foundation - Project RiMedRi CUP G73F12000150004 Disclosures No relevant conflicts of interest to declare.

scholarly journals Effect of crotamine, a cell-penetrating peptide, on blastocyst production and gene expression of in vitro fertilized bovine embryos

Zygote ◽  
2014 ◽  
Vol 24 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Iana S. Campelo ◽  
Alexsandra F. Pereira ◽  
Agostinho S. Alcântara-Neto ◽  
Natalia G. Canel ◽  
Joanna M.G. Souza-Fabjan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Control Group ◽  
Cell Penetrating Peptide ◽  
Mrna Levels ◽  
Bovine Embryos ◽  
Control Groups ◽  
Cell Penetrating ◽  
A Cell ◽  
And Control

SummaryThe present study investigated the effects of crotamine, a cell-penetrating peptide from rattlesnake venom, at different exposure times and concentrations, on both developmental competence and gene expression (ATP1A1, AQP3, GLUT1 and GLUT3) of in vitro fertilized (IVF) bovine embryos. In Experiment 1, presumptive zygotes were exposed to 0.1 μM crotamine for 6, 12 or 24 h and control groups (vehicle and IVF) were included. In Experiment 2, presumptive zygotes were exposed to 0 (vehicle), 0.1, 1 and 10 μM crotamine for 24 h. Additionally, to visualize crotamine uptake, embryos were exposed to rhodamine B-labelled crotamine and subjected to confocal microscopy. In Experiment 1, no difference (P > 0.05) was observed among different exposure times and control groups for cleavage and blastocyst rates and total cells number per blastocyst. Within each exposure time, mRNA levels were similar (P > 0.05) in embryos cultured with or without crotamine. In Experiment 2, concentrations as high as 10 μM crotamine did not affect (P > 0.05) the blastocyst rate. Crotamine at 0.1 and 10 μM did not alter mRNA levels when compared with the control (P > 0.05). Remarkably, only 1 μM crotamine decreased both ATP1A1 and AQP3 expression levels relative to the control group (P < 0.05). Also, it was possible to visualize the intracellular localization of crotamine. These results indicate that crotamine can translocate intact IVF bovine embryos and its application in the culture medium is possible at concentrations from 0.1–10 μM for 6–24 h.

scholarly journals eNOS Gene Variant in Patients with Coronary Artery Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Milad Abolhalaj ◽  
Mahsa M. Amoli ◽  
Parvin Amiri
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Enos Gene ◽  
Enos Expression ◽  
Vntr Polymorphism ◽  
The Difference ◽  
Artery Disease ◽  
And Control ◽  
Endothelial Nitric Oxide

Subject & Aim. Endothelial nitric oxide synthase (eNOS) is one of the most important candidate genes in CAD. A functional polymorphism within eNOS gene is a 27 bp VNTR on its intron 4 which has been shown to be associated with various diseases. In this study we investigated eNOS VNTR polymorphism in addition to eNOS gene expression profile in patients with CAD. Material and Methods. The study comprised patients with angiographically confirmed CAD (CAD+) and individuals with normal coronary as CAD−. eNOS VNTR polymorphism frequencies were determined in both groups. In addition eNOS gene expression profile was examined using a quantitative real-time PCR. Results. We have found that aa genotype was significantly increasing the risk of CAD in our patients (aa versus ab + bb, , ; 95% CI: = 0.98 to 16.2). The differences in eNOS expression were not significant between patients and normal group; however in CAD+ patients eNOS expression was higher than the expression level of patients carrying other genotypes (). Conclusion. We have observed that eNOS gene polymorphism was associated with CAD in angiography-confirmed patients. However, the difference in eNOS gene expression was not statistically significant between patients and control which might be due to the contribution of other confounding factors which require further investigations.

scholarly journals T Cells Help To Amplify Inflammatory Responses Induced by Salmonella enterica Serotype Typhimurium in the Intestinal Mucosa

2008 ◽  
Vol 76 (5) ◽  
pp. 2008-2017 ◽  
Author(s):  
Ivan Godinez ◽  
Takeshi Haneda ◽  
Manuela Raffatellu ◽  
Michael D. George ◽  
Tatiane A. Paixão ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Salmonella Enterica ◽  
Inflammatory Responses ◽  
Mrna Levels ◽  
Genes Encoding ◽  
Ifn Γ ◽  
Cecal Mucosa

ABSTRACT Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T-cell-derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of genes encoding gamma interferon (IFN-γ), interleukin-22 (IL-22), and IL-17 were detected by quantitative real-time PCR. Furthermore, the mRNA levels of genes whose expression is induced by IFN-γ, IL-22, or IL-17, including genes encoding macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (Nos2), lipocalin-2 (Lcn2), MIP-1α, MIP-1β, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this proinflammatory gene expression profile, we depleted T cells by using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin-pretreated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils, and a marked reduction in mRNA levels of Ifn-γ, Il-22, Il-17, Nos2, Lcn2, and Kc. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile

2020 ◽  
Vol 105 (12) ◽  
pp. e4577-e4592
Author(s):  
Jasna Metovic ◽  
Chiara Vignale ◽  
Laura Annaratone ◽  
Simona Osella-Abate ◽  
Francesca Maletta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Adverse Outcome ◽  
Control Group ◽  
Related Gene ◽  
Molecular Features ◽  
Immune Related Gene ◽  
Oncocytic Variant ◽  
Poorly Differentiated

Abstract Background Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). Methods A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction. Results Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype. Conclusions Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.

Translocation t(14;19)(q32;q13) Is a Rare Abnormality in CLL and Associated with Trisomy 12, an Unmutated IgVH Status and a Distinct Gene Expression Profile.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4703-4703
Author(s):  
Claudia Haferlach ◽  
Sonja Rauhut ◽  
Sylvia Merk ◽  
Frank Dicker ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Differentially Expressed Genes ◽  
Expression Profile ◽  
Chromosomal Aberrations ◽  
Differentially Expressed ◽  
Chain Gene ◽  
Distinct Gene ◽  
Distinct Gene Expression Profile ◽  
Trisomy 12

Abstract Chronic lymphocytic leukemia (CLL) is a genetically heterogeneous disease. Recently, several genetic aberrations have been identified that allow to distinguish different biological subgroups within CLL. Translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 is a rare but recurrent abnormality in CLL and still poorly described. Based on karyotype data we identified 12 cases with t(14;19)(q32;q13) in a cohort of 1051 CLL (1.1%). In all these cases 1 to 10 chromosomal aberrations were observed in addition to t(14;19) (median: 3). Recurring accompanying aberrations were: +12 (n=8), loss of 18p (n=2), and gain of 10q (n=2). Interestingly, trisomy 12 is also the most frequent additional abnormality in CLL with t(14;18)(q32;q21). Remarkably, neither 13q deletions nor 11q deletions which are frequently observed in CLL overall, were found in addition to t(14;19). A TP53-deletion and a 6q21 deletion were observed in one case each. In 8/12 cases the mutation status of the immunoglobulin variable heavy chain gene (IgVH) was available. All 8 cases showed an unmutated IgVH status. Gene expression analysis (Affymetrix, HG U133 Plus 2.0) was performed in 9 cases with t(14;19) and compared to 44 cases with CLL comprising various chromosome aberrations excluding t(14;19). Using 10fold cross validation resulted in an assignment of 7 out of 9 cases with t(14;19) into the correct class, none of the cases without t(14;19) was classified into the t(14;19) group (accuracy 96%, sensitivity 78%, specificity 100%). Classification based on an independent test set led to comparable results (median accuracy 94%, sensitivity 67%, specificity 100%). The 10 most differentially expressed genes showing a higher expression in t(14;19)+ CLL were: TUBB6, CPSF6, RFC5, MAP3K8, CUGBP2, BCAT1, BCAT1, LOC647135, TSPAN13, SIGLEC6 and are involved in transition of mitotic cell cycle, DNA replication and RNA processing. The 10 most differentially expressed genes showing a lower expression in t(14;19)+ CLL were: LSR, APLP2, C2orf10, HS3ST1, LRRC32, PALM2-AKAP2, DFNB31, PDE4A, CTLA4, PDCD4 and are involved in signal transduction, apoptosis and immune response. In conclusion: t(14;19)(q32;q13) is a rare, recurrent chromosome abnormality in CLL. It is very frequently accompanied by additional chromosomal aberrations. The most frequent additional aberration is trisomy 12. t(14;19) is associated with an unmutated IgVH status. Comparable to other translocations leading to fusion genes it is associated with a distinct gene expression profile.

Sign in / Sign up

Export Citation Format

Share Document