Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy

2006 ◽  
Vol 27 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Sudarsan Rajan ◽  
Sarah S. Williams ◽  
Ganapathy Jagatheesan ◽  
Rafeeq P. H. Ahmed ◽  
Geraldine Fuller-Bicer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Microarray Analysis ◽  
Ventricular Hypertrophy ◽  
Molecular Mechanisms ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Differentially Expressed ◽  
Transgenic Mouse Models ◽  
Ventricular Tissue ◽  
Gene Transcripts

Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. We previously developed two transgenic mouse models that carry FHC-associated mutations in α-tropomyosin (TM): FHC α-TM175 mice show patchy areas of mild ventricular disorganization and limited hypertrophy, whereas FHC α-TM180 mice exhibit severe hypertrophy and fibrosis and die within 6 mo. To obtain a better understanding of the molecular mechanisms associated with the early onset of cardiac hypertrophy, we conducted a detailed comparative analysis of gene expression in 2.5-mo-old control, FHC α-TM175, and α-TM180 ventricular tissue. Results show that 754 genes (from a total of 22,600) were differentially expressed between the nontransgenic (NTG) and the FHC hearts. There are 178 differentially regulated genes between NTG and the FHC α-TM175 hearts, 388 genes are differentially expressed between NTG and FHC α-TM180 hearts, and 266 genes are differentially expressed between FHC α-TM175 and FHC α-TM180 hearts. Genes that exhibit the largest increase in expression belong to the “secreted/extracellular matrix” category, and those with the most significant decrease in expression are associated with “metabolic enzymes.” Confirmation of the microarray analysis was conducted by quantitative real-time PCR on gene transcripts commonly associated with cardiac hypertrophy.

scholarly journals Evaluation of Differential Gene Expression in Fluconazole-Susceptible and -Resistant Isolates of Candida albicans by cDNA Microarray Analysis

2002 ◽  
Vol 46 (11) ◽  
pp. 3412-3417 ◽  
Author(s):  
P. David Rogers ◽  
Katherine S. Barker
Keyword(s):  
Gene Expression ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Cell Stress ◽  
Differentially Expressed ◽  
Ergosterol Biosynthesis ◽  
Azole Resistance ◽  
Lipid Fatty Acid

ABSTRACT The opportunistic fungal pathogen Candida albicans is the major causative agent of oropharyngeal candidiasis (OPC) in AIDS. The development of azoles, such as fluconazole, for the treatment of OPC has proven effective except in cases where C. albicans develops resistance to fluconazole during the course of treatment. In the present study, we used microarray technology to examine differences in gene expression from a fluconazole-susceptible and a fluconazole-resistant well-characterized, clinically obtained matched set of C. albicans isolates to identify genes which are differentially expressed in association with azole resistance. Among genes found to be differentially expressed were those involved in amino acid and carbohydrate metabolism; cell stress, cell wall maintenance; lipid, fatty acid, and sterol metabolism; and small molecule transport. In addition to CDR1, which has previously been demonstrated to be associated with azole resistance, the drug resistance gene RTA3, the ergosterol biosynthesis gene ERG2, and the cell stress genes CRD2, GPX1, and IFD5 were found to be upregulated. Several genes, such as the mitochondrial aldehyde dehydrogenase gene ALD5, the glycosylphosphatidylinositol synthesis gene GPI1, and the iron transport genes FET34 and FTR2 were found to be downregulated. Further study of these differentially regulated genes is warranted to evaluate how they may be involved in azole resistance. In addition to these novel findings, we demonstrate the utility of microarray analysis for studying the molecular mechanisms of drug resistance in pathogenic organisms.

Insights into the seasonal adaptive mechanisms of Chinese alligators (Alligator sinensis) from transcriptomic analyses

2018 ◽  
Vol 66 (2) ◽  
pp. 93 ◽  
Author(s):  
Hongji Sun ◽  
Xianbo Zuo ◽  
Long Sun ◽  
Peng Yan ◽  
Fang Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Seasonal Adaptation ◽  
Cold Temperatures ◽  
Chinese Alligator ◽  
Adaptive Mechanisms ◽  
Alligator Sinensis

The Chinese alligator (Alligator sinensis) is an endemic and rare species in China, and is considered to be one of the most endangered vertebrates in the world. It is known to hibernate, an energy-saving strategy against cold temperatures and food deprivation. Changes in gene expression during hibernation remain largely unknown. To understand these complex seasonal adaptive mechanisms, we performed a comprehensive survey of differential gene expression in heart, skeletal muscle, and kidney of hibernating and active Chinese alligators using RNA-Sequencing. In total, we identified 4780 genes differentially expressed between the active and hibernating periods. GO and KEGG pathway analysis indicated the likely role of these differentially expressed genes (DEGs). The upregulated DEGs in the active Chinese alligator, CSRP3, MYG and PCKGC, may maintain heart and skeletal muscle contraction, transport and storage of oxygen, and enhance the body’s metabolism, respectively. The upregulated DEGs in the dormant Chinese alligator, ADIPO, CIRBP and TMM27, may improve insulin sensitivity and glucose/lipid metabolism, protect cells against harmful effects of cold temperature and hypoxia, regulate amino acid transport and uptake, and stimulate the proliferation of islet cells and the secretion of insulin. These results provide a foundation for understanding the molecular mechanisms of the seasonal adaptation required for hibernation in Chinese alligators, as well as effective information for other non-model organisms research.

scholarly journals Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

2020 ◽  
Author(s):  
Na Li ◽  
Ru-feng Bai ◽  
Chun Li ◽  
Li-hong Dang ◽  
Qiu-xiang Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Healing Process ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Wound Age ◽  
Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

scholarly journals Gene expression vs. sequence divergence: comparative transcriptome sequencing among natural Rhinolophus ferrumequinum populations with different acoustic phenotypes

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Hanbo Zhao ◽  
Hui Wang ◽  
Tong Liu ◽  
Sen Liu ◽  
Longru Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Geographic Variation ◽  
Molecular Mechanisms ◽  
Sequence Divergence ◽  
Orthologous Gene ◽  
Differentially Expressed ◽  
Nucleotide Polymorphisms ◽  
Genetic Lineages ◽  
Rhinolophus Ferrumequinum ◽  
Horseshoe Bat

Abstract Background Although the sensory drive hypothesis can explain the geographic variation in echolocation frequencies of some bat species, the molecular mechanisms underlying this phenomenon are still unclear. The three lineages of greater horseshoe bat (Rhinolophus ferrumequinum) in China (northeast, central-east, and southwest) have significant geographic variation in resting frequencies (RF) of echolocation calls. Because their cochleae have an acoustic fovea that is highly sensitive to a narrow range of frequencies, we reported the transcriptomes of cochleae collected from three genetic lineages of R. ferrumequinum, which is an ideal organism for studying geographic variation in echolocation signals, and tried to understand the mechanisms behind this bat phenomenon by analyzing gene expression and sequence variation. Results A total of 8190 differentially expressed genes (DEGs) were identified. We identified five modules from all DEGs that were significantly related to RF or forearm length (FL). DEGs in the RF-related modules were significantly enriched in the gene categories involved in neural activity, learning, and response to sound. DEGs in the FL-related modules were significantly enriched in the pathways related to muscle and actin functions. Using 21,945 single nucleotide polymorphisms, we identified 18 candidate unigenes associated with hearing, five of which were differentially expressed among the three populations. Additionally, the gene ERBB4, which regulates diverse cellular processes in the inner ear such as cell proliferation and differentiation, was in the largest module. We also found 49 unigenes that were under positive selection from 4105 one-to-one orthologous gene pairs between the three R. ferrumequinum lineages and three other Chiroptera species. Conclusions The variability of gene expression and sequence divergence at the molecular level might provide evidence that can help elucidate the genetic basis of geographic variation in echolocation signals of greater horseshoe bats.

scholarly journals The Expression of Human Placental Genes Related to Carotenoid/retinoid Metabolism and Pathways (P02-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xiaoming Gong ◽  
Lewis Rubin
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Fetal Development ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Retinoid Metabolism ◽  
Expression Of Genes ◽  
Β Carotene

Abstract Objectives Carotenoid/retinoids status and metabolism are essential for normal placental and fetal development. Both deficiencies and excess of retinoids and some carotenoids are associated with adverse pregnancy outcomes, such as preeclampsia and preterm birth. A group of important genes involved in regulating carotenoid/retinoid metabolism and maternal to fetal transfer in human placenta. The objective of this study is to analyze (a) the expression of genes critical for regulating carotenoid/retinoid metabolism and maternal-fetal transport in human trophoblasts and (b) placental transcriptional profiles of these pathways in response to carotenoid exposure. Methods Human cytotrophoblasts (CTBs) were isolated from term placentas. CTB RNA was used to analyze the expression of genes involved in carotenoid/retinoid metabolism and pathways by qRT-PCT. First trimester-like trophoblasts (HTR-8/SVneo) were treated with either β-carotene or lycopene. RNAs were isolated and gene expression were analyzed by DNA microarrays. Results Human CTBs express retinoid metabolism and pathways-related genes, including Stra6, Lrat, Rdh5, Rdh10, Aldh1a1, Aldh1a2, Aldh1a3, Aldh8a1, Cyp26a1, and Cyp26b1, but not carotenoid metabolism genes, BCO1 and BCO2. Microarray analysis of placental gene expression profile revealed a total of 872 and 756 differentially expressed genes, respectively, compared to the control. Gene set enrichment analysis and functional annotation clustering was performed to characterize the genes differentially expressed in either β-carotene or lycopene-treated HTR-8/SVneo cells. Many known retinoid metabolism related genes and genes involved in regulation of retinoid signaling were found, and the expression profiles of these genes were markedly different in response to β-carotene treatments. Finally, the qRT-PCR and microarray analysis results showed similar gene expression patterns of carotenoid/retinoid metabolism and pathways. Conclusions These findings suggest that placental expression of genes involved in retinoid metabolism and transport in trophoblasts is critical for regulating retinoid homeostasis during placental and fetal development. Carotenoid exposure in early placental development, significantly modify the placenta gene expression related to retinoid pathways and maternal to fetal transfer. Funding Sources NIH HD421174.

scholarly journals The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes

2007 ◽  
Vol 27 (11) ◽  
pp. 4082-4092 ◽  
Author(s):  
Andrew J. Bingham ◽  
Lezanne Ooi ◽  
Lukasz Kozera ◽  
Edward White ◽  
Ian C. Wood
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cardiac Hypertrophy ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Ventricular Myocytes ◽  
Specific Gene ◽  
Histone H4 Acetylation ◽  
Repressor Element

ABSTRACT Cardiac hypertrophy is associated with a dramatic change in the gene expression profile of cardiac myocytes. Many genes important during development of the fetal heart but repressed in the adult tissue are reexpressed, resulting in gross physiological changes that lead to arrhythmias, cardiac failure, and sudden death. One transcription factor thought to be important in repressing the expression of fetal genes in the adult heart is the transcriptional repressor REST (repressor element 1-silencing transcription factor). Although REST has been shown to repress several fetal cardiac genes and inhibition of REST function is sufficient to induce cardiac hypertrophy, the molecular mechanisms employed in this repression are not known. Here we show that continued REST expression prevents increases in the levels of the BNP (Nppb) and ANP (Nppa) genes, encoding brain and atrial natriuretic peptides, in adult rat ventricular myocytes in response to endothelin-1 and that inhibition of REST results in increased expression of these genes in H9c2 cells. Increased expression of Nppb and Nppa correlates with increased histone H4 acetylation and histone H3 lysine 4 methylation of promoter-proximal regions of these genes. Furthermore, using deletions of individual REST repression domains, we show that the combined activities of two domains of REST are required to efficiently repress transcription of the Nppb gene; however, a single repression domain is sufficient to repress the Nppa gene. These data provide some of the first insights into the molecular mechanism that may be important for the changes in gene expression profile seen in cardiac hypertrophy.

scholarly journals Transcriptomic analysis of PPARα-dependent alterations during cardiac hypertrophy

2008 ◽  
Vol 36 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Pascal J. H. Smeets ◽  
Heleen M. de Vogel-van den Bosch ◽  
Peter H. M. Willemsen ◽  
Alphons P. Stassen ◽  
Torik Ayoubi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Lipid Metabolism ◽  
Cardiac Hypertrophy ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Left Ventricular ◽  
Transcriptomic Analysis ◽  
Differentially Expressed ◽  
Wild Type

Peroxisome proliferator-activated receptor (PPAR)α regulates lipid metabolism at the transcriptional level and modulates the expression of genes involved in inflammation, cell proliferation, and differentiation. Although PPARα has been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms and the nature of signaling pathways involved is fragmentary and incomplete. The aim of this study was to identify the processes and signaling pathways regulated by PPARα in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. PPARα−/− and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days, and left ventricular gene expression profile was determined with Affymetrix GeneChip Mouse Genome 430 2.0 arrays containing >45,000 probe sets. In unchallenged hearts, the mere lack of PPARα resulted in 821 differentially expressed genes, many of which are related to lipid metabolism and immune response. TAC resulted in a more pronounced cardiac hypertrophy and more extensive changes in gene expression (1,910 and 312 differentially expressed genes, respectively) in PPARα−/− mice than in wild-type mice. Many of the hypertrophy-related genes were related to development, signal transduction, actin filament organization, and collagen synthesis. Compared with wild-type hypertrophied hearts, PPARα−/− hypertrophied hearts revealed enrichment of gene clusters related to extracellular matrix remodeling, immune response, oxidative stress, and inflammatory signaling pathways. The present study therefore demonstrates that, in addition to lipid metabolism, PPARα is an important modulator of immune and inflammatory response in cardiac muscle.

scholarly journals Expression Profile of Circulating MicroRNAs in Dogs With Cardiac Hypertrophy: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Woong-Bin Ro ◽  
Min-Hee Kang ◽  
Doo-Won Song ◽  
Sung-Hun Lee ◽  
Hee-Myung Park
Keyword(s):  
Pilot Study ◽  
Cardiac Hypertrophy ◽  
Microarray Analysis ◽  
Expression Profile ◽  
Heart Diseases ◽  
Differentially Expressed ◽  
Serum Samples ◽  
Down Regulation ◽  
Circulating Micrornas ◽  
Healthy Dogs

This study aimed to identify the expression profile of circulating microRNAs in dogs with eccentric or concentric cardiac hypertrophy. A total of 291 microRNAs in serum samples of five dogs with myxomatous mitral valve degeneration (MMVD) and five dogs with pulmonic stenosis (PS) were compared with those of five healthy dogs using microarray analysis. Results of microarray analysis revealed up-regulation of cfa-miR-130b [fold change (FC) = 2.13, p = 0.014), down-regulation of cfa-miR-375 (FC = 1.51, p = 0.014), cfa-miR-425 (FC = 2.56, p = 0.045), cfa-miR-30d (FC = 3.02, p = 0.047), cfa-miR-151 (FC = 1.89, p = 0.023), cfa-miR-19b (FC = 3.01, p = 0.008), and cfa-let-7g (FC = 2.53, p = 0.015) in MMVD group which showed eccentric cardiac hypertrophy, up-regulation of cfa-miR-346 (FC = 2.74, p = 0.032), down-regulation of cfa-miR-505 (FC = 1.56, p = 0.016) in PS group which showed concentric cardiac hypertrophy, and down-regulation of cfa-miR-30c (FC = 3.45, p = 0.013 in MMVD group; FC = 3.31, p = 0.014 in PS group) and cfa-let-7b (FC = 11.42, p = 0.049 in MMVD group; FC = 5.88, p = 0.01 in PS group) in both MMVD and PS groups. In addition, the unsupervised hierarchical clustering of differentially expressed microRNAs in each group resulted in complete separation of healthy dogs from dogs with heart diseases. Therefore, eleven microRNAs among 291 microRNAs were identified as differentially expressed circulating microRNAs related to MMVD or PS in dogs. This pilot study demonstrates that the microRNAs identified in this study could be possible candidates for novel biomarker or therapeutic target related to cardiac hypertrophy in dogs.

scholarly journals Screening differentially expressed genes of pancreatic cancer between Mongolian and Han people using bioinformatics technology

2019 ◽  
Author(s):  
Jiasheng Xu ◽  
Kaili Liao ◽  
ZHONGHUA FU ◽  
ZHENFANG XIONG
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Gene Ontology ◽  
Differentially Expressed Genes ◽  
Microarray Analysis ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Tissue Samples ◽  
Multiple Difference

Abstract Objective: To screen and analyze differentially expressed genes in pancreatic carcinoma tissues taken from Mongolian and Han patients by Affymetrix Genechip. Methods: Pancreatic ductal cell carcinoma tissues were collected from the Mongolian and Han patients undergoing resection in the Second Affiliated Hospital of Nanchang University from March 2015 to May 2018 and the total RNA was extracted. Differentially expressed genes were selected from the total RNA qualified by Nanodrop 2000 and Agilent 2100 using Affymetrix and a cartogram was drawn; The gene ontology (GO) analysis and Pathway analysis were used for the collection and analysis of biological information of these differentially expressed genes. Finally, some differentially expressed genes were verified by real-time PCR. Results: Through the microarray analysis of gene expression, 970 differentially expressed genes were detected by comparing pancreatic cancer tissue samples between Mongolian and Han patients. A total of 257 genes were significantly up-regulated in pancreatic cancer tissue samples in Mongolian patients; while a total of 713 genes were down-regulated. In the Gene Ontology database, 815 differentially expressed genes were identified with clear GO classification, and CPB1 gene showed the highest increase in expression level (multiple difference: 31.76). The pathway analysis detected 28 signaling pathways that included these differentially expressed genes, involving a total of 178 genes. Among these pathways, the enrichment of differentially expressed genes in the FAK signaling pathway was the strongest and COL11A1 gene showed the highest multiple difference (multiple difference: 5.02). The expression of differentially expressed genes CPB1, COL11A1、ITGA4、BIRC3、PAK4、CPA1、CLPS、PIK3CG and HLA-DPA1 determined by real-time PCR were consistent with the results of gene microarray analysis. Conclusions: The results of microarray analysis of gene expression profiles showed that there are a large number of differentially expressed genes in pancreatic cancer tissue samples comparing Mongolian and Han population. These genes are closely related to the cell proliferation, differentiation, invasion, metastasis and multi-drug resistance in pancreatic cancer. They are also involved in the regulation of multiple important signaling pathways in organisms.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

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