scholarly journals Molecular basis of glucocorticoid action

2005 ◽  
Vol 133 (Suppl. 1) ◽  
pp. 61-66 ◽  
Author(s):  
Nevena Ribarac-Stepic ◽  
Snezana Djurica ◽  
Zorica Zakula ◽  
Goran Koricanac ◽  
Dragoslav Milosevic
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Receptor Protein ◽  
Clinical Aspects ◽  
Signal Pathways ◽  
Specific Cell ◽  
Cell Functions ◽  
Receptor Complexes ◽  
Glucocorticoid Action

Glucocorticoid hormones are involved in regulation of cell processes and coordinate physiological response to diverse signals. These hormones, through interaction with specific intracellular receptors, coordinate components of physiological repertoires by activating the expression of gene networks. Thus hormone-receptor complexes may function as key constituent in regulation of specific cell functions as well as in provoking differentiation in already determined cells. Analysis of steroid receptors are important for understanding of molecular details of transcriptional control as well as providing the insight as to how an individual transcriptional factor such as glucocorticoid receptor, contributes to cell identity and function. The purpose of this review is to establish the general molecular mechanism of glucocorticoid action and mechanism associated hormonereceptor complexes with the control of differential patterns (i.e. ?positive? and ?negative?) of gene expression. One of the examples of two signal pathways regulating opposite gene expression are NF-?B and GR-mediated signal pathways. These pathways have important and opposite roles in the immune function. NF-?B is transcription factor which induces the expression of many genes that participate in immune and inflamatory response, while GR is transcription factor that serves as antiinflammatory agent and immune suppressor. Their interactions within the cell, although not yet completely understood, appear to be an important, possibly even the primary mechanism of immune homeostasis. It has not been established that glucocorticoid sensitivity can be caused by mechanisms other than changes of GR number and properties, although recent studies have indicated that receptor isoforms and transcriptional factors may modulate glucocorticoid responsiveness by interacting with receptor protein or directly at the site of DNA binding. The aim of this review is also to describe the role of glucocorticoid receptors in mechanism of glucocorticoid action on cell functions, including immune responses, as well as to present emerging issues on clinical aspects of molecular mechanisms of glucocorticoid action.

Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 114-138 ◽  
Author(s):  
R. E. Scharf
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Platelet Membrane ◽  
Clinical Aspects ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Membrane Expression ◽  
Receptor Complexes ◽  
Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

scholarly journals Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (1): specific signatures of stromal, glandular and luminal epithelial cells

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wiruntita Chankeaw ◽  
Sandra Lignier ◽  
Christophe Richard ◽  
Theodoros Ntallaris ◽  
Mariam Raliou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Localization ◽  
Expression Profiles ◽  
Cell Types ◽  
Molecular Signature ◽  
Receptor Protein ◽  
Specific Gene ◽  
Specific Cell ◽  
Biological Processes ◽  
Endometrial Cells

Abstract Background A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle. Results In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process. Conclusion The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.

scholarly journals The ETS-Domain Transcription Factor Elk-1 Regulates COX-2 Gene Expression and Inhibits Glucose-Stimulated Insulin Secretion in the Pancreaticβ-Cell Line INS-1

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Xiong-Fei Zhang ◽  
Yi Zhu ◽  
Wen-Biao Liang ◽  
Jing-Jing Zhang
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Insulin Secretion ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Cell Dysfunction ◽  
Cox 2 ◽  
Glucose Stimulated Insulin Secretion

Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreaticβ-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impairβ-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. We previously demonstrated that transcription factor Elk-1 significantly upregulated COX-2 gene promoter activity. In this report, we used pancreaticβ-cell line (INS-1) to explore the relationships between Elk-1 and COX-2. We first investigated the effects of Elk-1 on COX-2 transcriptional regulation and expression in INS-1 cells. We thus undertook to study the binding of Elk-1 to its putative binding sites in the COX-2 promoter. We also analysed glucose-stimulated insulin secretion (GSIS) in INS-1 cells that overexpressed Elk-1. Our results demonstrate that Elk-1 efficiently upregulates COX-2 expression at least partly through directly binding to the −82/−69 region of COX-2 promoter. Overexpression of Elk-1 inhibits GSIS in INS-1 cells. These findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreaticβ-cell. Moreover, Elk-1, the transcriptional regulator of COX-2 expression, will be a potential target for the prevention ofβ-cell dysfunction mediated by PGE2.

scholarly journals The grapevine R2R3-type MYB transcription factor VdMYB1 positively regulates defense responses by activating the stilbene synthase gene 2 (VdSTS2)

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yihe Yu ◽  
Dalong Guo ◽  
Guirong Li ◽  
Yingjun Yang ◽  
Guohai Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Plant Protection ◽  
Defense Responses ◽  
Stilbene Synthase ◽  
Myb Transcription Factor ◽  
Wide Range ◽  
Grapevine Leaves

Abstract Background Resveratrol is a naturally occurring plant stilbene that exhibits a wide range of valuable biological and pharmacological properties. Although the beneficial effects of trans-resveratrol to human health and plant protection against fungal pathogens and abiotic stresses are well-established, yet little is known about the molecular mechanisms regulating stilbene biosynthesis in plant defense progress. Results Here, we cloned and identified the Chinese wild grape (Vitis davidii) R2R3-MYB transcription factor VdMYB1, which activates defense responses against invading pathogen. VdMYB1 transcripts were significantly upregulated after inoculation with the grapevine powdery mildew fungus Erysiphe necator (Schw.) Burr. Transient expression analysis using onion epidermal cells and Arabidopsis thaliana protoplasts showed that VdMYB1 was localized in the nucleus. Yeast one-hybrid assays revealed that VdMYB1 acts as a transcriptional activator. Grapevine leaves transiently overexpressing VdMYB1 showed a lower number of fungal conidiophores compared with wild-type leaves. Overexpression of VdMYB1 in grapevine leaves did not alter the expression of genes in salicylic acid- and jasmonate-dependent pathways, but affected the expression of stilbene synthase (STS) genes, key regulators of flavonoid metabolism. Results of electrophoretic mobility shift assays and in vivo transcriptional activation assays showed that VdMYB1 binds to the MYB binding site (MYBBS) in the STS2 gene promoter, thus activating STS2 transcription. In heterologous expression assays using tobacco leaves, VdMYB1 activated STS2 gene expression and increased the accumulation of resveratrol. Conclusions Our study showed that VdMYB1 activates STS2 gene expression to positively regulate defense responses, and increases the content of resveratrol in leaves.

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 Specific Inhibition of Interferon Signal Transduction Pathways by Adenoviral Infection

2001 ◽  
Vol 276 (50) ◽  
pp. 47136-47142 ◽  
Author(s):  
Theresa D. Joseph ◽  
Dwight C. Look
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Airway Epithelial Cells ◽  
Signal Transducer ◽  
Airway Epithelial ◽  
Complex Assembly ◽  
Ifn Γ

Adenoviral evolution has generated strategies to resist host cell antiviral systems, but molecular mechanisms for evasion of interferon (IFN) effects by adenoviruses during late-phase infection are poorly defined. In this study, we examined adenovirus type 5 (AdV) effects on IFN-γ-dependent gene expression and Janus family kinase-signal transducer and activator of transcription signaling components in human tracheobronchial epithelial cells. We found that AdV infection specifically inhibited IFN-γ-dependent gene expression in airway epithelial cells without evidence of epithelial cell injury or generation of a soluble extracellular inhibitor. Furthermore, infection with AdV for 18–24 h blocked phosphorylation/activation of the Stat1 transcription factor that regulates IFN-γ-dependent genes. Although AdV also inhibited IFN-α-dependent phosphorylation of Stat1 and Stat2, interleukin-4-dependent phosphorylation of the related transcription factor Stat6 was not affected, indicating that the virus selectively affected specific signaling pathways. Our results indicate that AdV inhibition of the IFN-γ signal transduction cascade occurs through loss of ligand-induced receptor complex assembly and consequent component phosphorylation and suggest that lack of complex assembly is due to decreased expression of the IFN-γR2 chain of the IFN-γ receptor. IFN-γR2 is required at an early step in Janus family kinase-signal transducer and activator of transcription pathway activation and is expressed at low levels in airway epithelial cells, supporting the concept that adenoviral down-regulation of the level of this IFN-γ receptor component allows for persistent modulation of IFN-γ-dependent gene expression.

scholarly journals Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells

2019 ◽  
Author(s):  
Arnav Moudgil ◽  
Michael N. Wilkinson ◽  
Xuhua Chen ◽  
June He ◽  
Alex J. Cammack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Single Cell ◽  
Binding Sites ◽  
Expression Profiles ◽  
Single Cells ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Specific Cell

AbstractIn situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.

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.

scholarly journals Interplay between the androgen receptor signaling axis and microRNAs in prostate cancer

2019 ◽  
Vol 26 (5) ◽  
pp. R237-R257 ◽  
Author(s):  
Rayzel C Fernandes ◽  
Theresa E Hickey ◽  
Wayne D Tilley ◽  
Luke A Selth
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Transcription Factor ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Clinical Applications ◽  
Cancer Growth ◽  
Androgen Receptor Signaling ◽  
Resistance To Therapy ◽  
Signaling Axis

The androgen receptor (AR) is a ligand-activated transcription factor that drives prostate cancer. Since therapies that target the AR are the mainstay treatment for men with metastatic disease, it is essential to understand the molecular mechanisms underlying oncogenic AR signaling in the prostate. miRNAs are small, non-coding regulators of gene expression that play a key role in prostate cancer and are increasingly recognized as targets or modulators of the AR signaling axis. In this review, we examine the regulation of AR signaling by miRNAs and vice versa and discuss how this interplay influences prostate cancer growth, metastasis and resistance to therapy. Finally, we explore the potential clinical applications of miRNAs implicated in the regulation of AR signaling in this prevalent hormone-driven disease.

scholarly journals The biological characteristics of transcription factors AP-2α and AP-2γ and their importance in various types of cancers

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Damian Kołat ◽  
Żaneta Kałuzińska ◽  
Andrzej K. Bednarek ◽  
Elżbieta Płuciennik
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Cancer Tissue ◽  
Diagnostic Biomarkers ◽  
Oncological Patients ◽  
Wide Range ◽  
Non Coding Rnas

Abstract The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.

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