scholarly journals A bioinformatics approach for identifying potential molecular mechanisms and key genes involved in COVID-19 associated cardiac remodeling

Gene Reports ◽  
2021 ◽  
pp. 101246
Author(s):  
Hamid Ceylan
Keyword(s):  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Key Genes

Effect of cortisol on neurophysin I/oxytocin and peptidyl glycine-α-amidating mono-oxygenase mRNA expression in bovine luteal and granulosa cells

2013 ◽  
Vol 16 (2) ◽  
pp. 231-239
Author(s):  
A. Ziolkowska ◽  
J. Mlynarczuk ◽  
J. Kotwica
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Oestrous Cycle ◽  
Luteal Cells ◽  
Ru 486 ◽  
Ovarian Cells ◽  
Key Genes ◽  
Ovary Function

Abstract Cortisol stimulates the synthesis and secretion of oxytocin (OT) from bovine granulosa and luteal cells, but the molecular mechanisms of cortisol action remain unknown. In this study, granulosa cells or luteal cells from days 1-5 and 11-15 of the oestrous cycle were incubated for 4 or 8 h with cortisol (1x10-5, 1x10-7 M). After testing cell viability and hormone secretion (OT, progesterone, estradiol), we studied the effect of cortisol on mRNA expression for precursor of OT (NP-I/OT) and peptidyl glycine-α-amidating mono-oxygenase (PGA). The influence of RU 486 (1x10-5 M), a progesterone receptor blocker and inhibitor of the glucocorticosteroid receptor (GR), on the expression for both genes was tested. Cortisol increased the mRNA expression for NP-I/OT and PGA in granulosa cells and stimulated the expression for NP-I/OT mRNA in luteal cells obtained from days 1-5 and days 11-15 of the oestrous cycle. Expression for PGA mRNA was increased only in luteal cells from days 11-15 of the oestrous cycle. In addition, RU 486 blocked the cortisol-stimulated mRNA expression for NP-I/OT and PGA in both types of cells. These data suggest that cortisol affects OT synthesis and secretion in bovine ovarian cells, by acting on the expression of key genes, that may impair ovary function.

scholarly journals Screen Key Genes Associated with Distraction-Induced Osteogenesis of Stem Cells Using Bioinformatics Methods

2021 ◽  
Vol 22 (12) ◽  
pp. 6505
Author(s):  
Jishizhan Chen ◽  
Jia Hua ◽  
Wenhui Song
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Negative Control ◽  
Gene Set Enrichment Analysis ◽  
Venn Diagram ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Two Samples ◽  
Key Genes

Applying mesenchymal stem cells (MSCs), together with the distraction osteogenesis (DO) process, displayed enhanced bone quality and shorter treatment periods. The DO guides the differentiation of MSCs by providing mechanical clues. However, the underlying key genes and pathways are largely unknown. The aim of this study was to screen and identify hub genes involved in distraction-induced osteogenesis of MSCs and potential molecular mechanisms. Material and Methods: The datasets were downloaded from the ArrayExpress database. Three samples of negative control and two samples subjected to 5% cyclic sinusoidal distraction at 0.25 Hz for 6 h were selected for screening differentially expressed genes (DEGs) and then analysed via bioinformatics methods. The Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The protein–protein interaction (PPI) network was visualised through the Cytoscape software. Gene set enrichment analysis (GSEA) was conducted to verify the enrichment of a self-defined osteogenic gene sets collection and identify osteogenic hub genes. Results: Three hub genes (IL6, MMP2, and EP300) that were highly associated with distraction-induced osteogenesis of MSCs were identified via the Venn diagram. These hub genes could provide a new understanding of distraction-induced osteogenic differentiation of MSCs and serve as potential gene targets for optimising DO via targeted therapies.

NRSF-GNAO1-CaMK2 axis exacerbates cardiac remodeling and progresses heart failure by impairing Ca2+ homeostasis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Inazumi ◽  
K Kuwahara ◽  
Y Kuwabara ◽  
Y Nakagawa ◽  
H Kinoshita ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Knockout Mice ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Systolic Function ◽  
Dominant Negative Mutant ◽  
Funding Source

Abstract Background In the development of heart failure, pathological intracellular signaling reactivates fetal cardiac genes, which leads to maladaptive remodeling and cardiac dysfunction. We previously reported that a transcriptional repressor, neuron restrictive silencer factor (NRSF) represses fetal cardiac genes and maintains normal cardiac function under normal conditions, while hypertrophic stimuli de-repress this NRSF mediated repression via activation of CaMKII. Molecular mechanisms by which NRSF maintains cardiac systolic function remains to be determined, however. Purpose To elucidate how NRSF maintains normal cardiac homeostasis and identify the novel therapeutic targets for heart failure. Methods and results We generated cardiac-specific NRSF knockout mice (NRSF cKO), and found that these NRSF cKO showed cardiac dysfunction and premature deaths accompanied with lethal arrhythmias, as was observed in our previously reported cardiac-specific dominant-negative mutant of NRSF transgenic mice (dnNRSF-Tg). By cDNA microarray analysis of dnNRSF-Tg and NRSF-cKO, we identified that expression of Gnao1 gene encoding Gαo, a member of inhibitory G proteins, was commonly increased in ventricles of both types of mice. ChIP-seq analysis, reporter assay and electrophoretic mobility shift assay identified that NRSF transcriptionally regulates Gnao1 gene expression. Genetic Knockdown of Gαo in dnNRSF-Tg and NRSF-cKO by crossing these mice with Gnao1 knockout mice ameliorated the reduced systolic function, increased arrhythmogenicity and reduced survival rates. Transgenic mice expressing a human GNAO1 in their hearts (GNAO1-Tg) showed progressive cardiac dysfunction with cardiac dilation. Ventricles obtained from GNAO1-Tg have increased phosphorylation level of CaMKII and increased expression level of endogenous mouse Gnao1 gene. These data suggest that increased cardiac expression of Gαo is sufficient to induce pathological Ca2+-dependent signaling and cardiac dysfunction, and that Gαo forms a positive regulatory circuit with CaMKII and NRSF. Electrophysiological analysis in ventricular myocytes of dnNRSF-Tg revealed that impaired Ca2+ handling via alterations in localized L-type calcium channel (LTCC) activities; decreased T-tubular and increased surface sarcolemmal LTCC activities, underlies Gαo-mediated cardiac dysfunction. Furthermore, we also identified increased expression of Gαo in ventricles of two different heart failure mice models, mice with transverse aortic constriction and mice carrying a mutant cardiac troponin T, and confirmed that genetic reduction of Gαo prevented the progression of cardiac dysfunction in both types of mice. Conclusions Increased expression of Gαo, induced by attenuation of NRSF-mediated repression forms a pathological circuit via activation of CaMKII. This circuit exacerbates cardiac remodeling and progresses heart failure by impairing Ca2+ homeostasis. Gαo is a potential therapeutic target for heart failure. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grants-in –Aid for Scientific Research from the Japan Society for the Promotion of Science

scholarly journals Elucidation of molecular mechanisms of flower form development in tree peony ( Paeonia suffriticosa ) through comparative transcriptome analysis of floral parts

2019 ◽  
Author(s):  
Jiuxing Lu ◽  
Yun Zheng ◽  
Haoning Wang ◽  
Zheng Wang ◽  
Yonghua Li ◽  
...  
Keyword(s):  
Woody Plants ◽  
Molecular Mechanisms ◽  
High Expression ◽  
Limited Information ◽  
Mads Box ◽  
Mads Box Genes ◽  
Tree Peony ◽  
Expression Levels ◽  
Key Genes ◽  
Flower Form

Abstract Background: Tree peony (Paeonia suffruticasa) is an economically, medicinally ornamentally important woody flowering woody plants in East Asia and is a common also ornamental shrub in Europe and North America. It is well known and prized for their beautiful flowers in many different forms. Samen petalody has been shown to be the most effective way to modify flower forms. However, there is limited information on the molecular mechanisms of stamen petalody and flower form formation in tree peony.Results: In this study, RNA sequencing was used to assemble and annotate the unigenes in the tree peony to identify the critical genes related to flower parts formation and verify the key genes in different flower forms of tree peony cultivar. A total of 76,007 high quality unigenes were assembled and 30,505 were successfully annotated. A total of 1,833 TFs were identified in our study, among them 16 MADS-box genes were found and characterized. Six key genes were selected to verity their functions in stamen petalody. AG and SEP showed high expression level in carpals and sepals separately both in stamen petalody group and non-stamen petalody groups. PI and AP3 showed high expression levels in inter-petals in stamen petalody groups than in staments in non-stamen petalody.Conclusion: Sixteen MADS-box genes were identified for the first time in tree peony through RNA-seq method. We identified six key genes based on their differential expression levels in different flower parts. These six key genes represented all categories in the ABCDE model to verify the functions in stamen petalody. PI and AP3 were verified to likely play important roles in regulating stamen petalody in tree peony. Our study has helped establish the flower development model in tree peony, identified key molecular mechanisms in the development of different flower forms, and provided valuable information in improving genetic diversity of tree peony and many other woody plants.

scholarly journals Identification of Hypoxia-Related Differentially Expressed Genes and Construction of the Clinical Prognostic Predictor in Hepatocellular Carcinoma by Bioinformatic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hao Guo ◽  
Jing Zhou ◽  
Yanjun Zhang ◽  
Zhi Wang ◽  
Likun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Model ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Prognostic Predictor ◽  
Key Genes

Background. Hypoxia closely relates to malignant progression and appears to be prognostic for outcome in hepatocellular carcinoma (HCC). Our research is aimed at mining the hypoxic-related genes (HRGs) and constructing a prognostic predictor (PP) model on clinical prognosis in HCC patients. Methods. RNA-sequencing data about HRGs and clinical data of patients with HCC were obtained from The Cancer Genome Atlas (TCGA) database portal. Differentially expressed HRGs between HCC and para-carcinoma tissue samples were obtained by applying the Wilcox analysis in R statistical software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene functional enrichment analyses. Then, the patients who were asked to follow up for at least one month were enrolled in the following study. Cox proportional risk regression model was applied to obtain key HRGs which related to overall survival (OS) in HCC. PP was constructed and defined, and the accuracy of PP was validated by constructing the signature in a training set and validation set. Connectivity map (CMap) was used to find potential drugs, and gene set cancer analysis (GSCA) was also performed to explore the underlying molecular mechanisms. Results. Thirty-seven differentially expressed HRGs were obtained. It contained 28 upregulated and 9 downregulated genes. After the univariate Cox regression model analysis, we obtained 27 prognosis-related HRGs. Of these, 25 genes were risk factors for cancer, and 2 genes were protective factors. The PP was composed by 12 key genes (HDLBP, SAP30, PFKP, DPYSL4, SLC2A1, HMOX1, PGK1, ERO1A, LDHA, ENO2, SLC6A6, and TPI1). GSCA results showed the overall activity of these 12 key genes in 10 cancer-related pathways. Besides, CMap identified deferoxamine, crotamiton, talampicillin, and lycorine might have effects with HCC. Conclusions. This study firstly reported 12 prognostic HRGs and constructed the model of the PP. This comprehensive research of multiple databases helps us gain insight into the biological properties of HCC and provides deferoxamine, crotamiton, talampicillin, and lycorine as potential drugs to fight against HCC.

scholarly journals Transcriptome Analysis Reveals Key Seed-Development Genes in Common Buckwheat (Fagopyrum esculentum)

2019 ◽  
Vol 20 (17) ◽  
pp. 4303 ◽  
Author(s):  
Hongyou Li ◽  
Qiuyu Lv ◽  
Jiao Deng ◽  
Juan Huang ◽  
Fang Cai ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Seed Development ◽  
Seed Size ◽  
Molecular Mechanisms ◽  
Signal Transduction Pathway ◽  
Fagopyrum Esculentum ◽  
Rna Seq ◽  
Common Buckwheat ◽  
Size Change ◽  
Key Genes

Seed development is an essential and complex process, which is involved in seed size change and various nutrients accumulation, and determines crop yield and quality. Common buckwheat (Fagopyrum esculentum Moench) is a widely cultivated minor crop with excellent economic and nutritional value in temperate zones. However, little is known about the molecular mechanisms of seed development in common buckwheat (Fagopyrum esculentum). In this study, we performed RNA-Seq to investigate the transcriptional dynamics and identify the key genes involved in common buckwheat seed development at three different developmental stages. A total of 4619 differentially expressed genes (DEGs) were identified. Based on the results of Gene Ontology (GO) and KEGG analysis of DEGs, many key genes involved in the seed development, including the Ca2+ signal transduction pathway, the hormone signal transduction pathways, transcription factors (TFs), and starch biosynthesis-related genes, were identified. More importantly, 18 DEGs were identified as the key candidate genes for seed size through homologous query using the known seed size-related genes from different seed plants. Furthermore, 15 DEGs from these identified as the key genes of seed development were selected to confirm the validity of the data by using quantitative real-time PCR (qRT-PCR), and the results show high consistency with the RNA-Seq results. Taken together, our results revealed the underlying molecular mechanisms of common buckwheat seed development and could provide valuable information for further studies, especially for common buckwheat seed improvement.

P4996The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A M C Koop ◽  
R F Videira ◽  
L Ottaviani ◽  
E M Poels ◽  
K W Van De Kolk ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Right Ventricular ◽  
Rna Sequencing ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Adult Heart ◽  
Hypertrophic Growth

Abstract Introduction Heart and neural crest derivatives expressed-2 (Hand2) has been identified as an important embryonic basic helix-loop-helix-transcription factor, with different functions in the development of the first and second heart field, from which the left and right ventricle originate, respectively. Our previous work revealed that Hand2, under conditions of left ventricular (LV) pressure overload, is re-expressed in the adult heart and activates a “fetal gene” program contributing to pathological cardiac remodeling. Ablation of cardiac expression of Hand2 resulted in protection to cardiac stress and attenuated maladaptive remodeling. Purpose In this study, we aimed at unraveling the role of Hand2 during cardiac remodeling in response to right ventricular (RV) pressure overload induced by pulmonary artery banding (PAB). Methods Hand2F/F and MCM− Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic and MRI derived hemodynamic parameters, and molecular remodelling were assessed for experimental groups and compared to sham-operated controls (Fig. 1a). RNA sequencing and gene ontology enrichment analysis were performed to compare the dysregulated genes between the pressure overloaded RV of the control and Hand2 knockout mice. Results After six weeks of increased pressure load (Fig. 1b), levels of Hand2 increased in the control banded animals but, as expected, remained absent in the knockout hearts (Fig. 1c). In contrast to the what was previously observed for the pressure overloaded LV, in the pressure loaded RV, Hand2 depletion resulted in more severe remodelling and dysfunction as reflected by increased hypertrophic growth, increased RV end-diastolic and end-systolic volumes as well as decreased RV ejection fraction (Fig. 1d–g). In addition, RNA sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. These include components of the extracellular matrix structure, collagen assembly and organization and several types of collagens. Genes associated with inflammation response, adhesion and muscle organization were also affected in the RV of the Hand2 KO mice (Fig. 1h). Figure 1 Conclusion Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressure overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodelling of the RV, in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure.

scholarly journals Unique expression patterns of multiple key genes associated with the evolution of mammalian flight

2014 ◽  
Vol 281 (1783) ◽  
pp. 20133133 ◽  
Author(s):  
Zhe Wang ◽  
Mengyao Dai ◽  
Yao Wang ◽  
Kimberly L. Cooper ◽  
Tengteng Zhu ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Genetic Changes ◽  
Multiple Gene ◽  
Membrane Growth ◽  
Complex Integration ◽  
Key Genes ◽  
Bat Wing

Bats are the only mammals capable of true flight. Critical adaptations for flight include a pair of dramatically elongated hands with broad wing membranes. To study the molecular mechanisms of bat wing evolution, we perform genomewide mRNA sequencing and in situ hybridization for embryonic bat limbs. We identify seven key genes that display unique expression patterns in embryonic bat wings and feet, compared with mouse fore- and hindlimbs. The expression of all 5′HoxD genes ( Hoxd9–13 ) and Tbx3 , six known crucial transcription factors for limb and digit development, is extremely high and prolonged in the elongating wing area. The expression of Fam5c , a tumour suppressor, in bat limbs is bat-specific and significantly high in all short digit regions (the thumb and foot digits). These results suggest multiple genetic changes occurred independently during the evolution of bat wings to elongate the hand digits, promote membrane growth and keep other digits short. Our findings also indicate that the evolution of limb morphology depends on the complex integration of multiple gene regulatory networks and biological processes that control digit formation and identity, chondrogenesis, and interdigital regression or retention.

scholarly journals Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction

2016 ◽  
Vol 213 (7) ◽  
pp. 1353-1374 ◽  
Author(s):  
Anta Ngkelo ◽  
Adèle Richart ◽  
Jonathan A. Kirk ◽  
Philippe Bonnin ◽  
Jose Vilar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mast Cells ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Troponin I ◽  
Heart Function ◽  
Ischemic Disease ◽  
Cardiomyocyte Contractility ◽  
The Impact

Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit–independent MC-deficient (Cpa3Cre/+) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca2+ desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force–Ca2+ interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators.

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