scholarly journals Leiomyoma and Myometrial Gene Expression Profiles and Their Responses to Gonadotropin-Releasing Hormone Analog Therapy

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1074-1096 ◽  
Author(s):  
Xiaoping Luo ◽  
Li Ding ◽  
Jingxia Xu ◽  
R. Stan Williams ◽  
Nasser Chegini
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Binding Protein ◽  
Expression Profiles ◽  
Primary Cultures ◽  
Time Dependent ◽  
Early Gene ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Gnrh Analog

Gene microarray was used to characterize the molecular environment of leiomyoma and matched myometrium during growth and in response to GnRH analog (GnRHa) therapy as well as GnRHa direct action on primary cultures of leiomyoma and myometrial smooth muscle cells (LSMC and MSMC). Unsupervised and supervised analysis of gene expression values and statistical analysis in R programming with a false discovery rate of P ≤ 0.02 resulted in identification of 153 and 122 differentially expressed genes in leiomyoma and myometrium in untreated and GnRHa-treated cohorts, respectively. The expression of 170 and 164 genes was affected by GnRHa therapy in these tissues compared with their respective untreated group. GnRHa (0.1 μm), in a time-dependent manner (2, 6, and 12 h), targeted the expression of 281 genes (P ≤ 0.005) in LSMC and MSMC, 48 of which genes were found in common with GnRHa-treated tissues. Functional annotations assigned these genes as key regulators of processes involving transcription, translational, signal transduction, structural activities, and apoptosis. We validated the expression of IL-11, early growth response 3, TGF-β-induced factor, TGF-β-inducible early gene response, CITED2 (cAMP response element binding protein-binding protein/p300-interacting transactivator with ED-rich tail), Nur77, growth arrest-specific 1, p27, p57, and G protein-coupled receptor kinase 5, representing cytokine, common transcription factors, cell cycle regulators, and signal transduction, at tissue levels and in LSMC and MSMC in response to GnRHa time-dependent action using real-time PCR, Western blotting, and immunohistochemistry. In conclusion, using different, complementary approaches, we characterized leiomyoma and myometrium molecular fingerprints and identified several previously unrecognized genes as targets of GnRHa action, implying that local expression and activation of these genes may represent features differentiating leiomyoma and myometrial environments during growth and GnRHa-induced regression.

scholarly journals Gene Expression Profiling of Leiomyoma and Myometrial Smooth Muscle Cells in Response to Transforming Growth Factor-β

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1097-1118 ◽  
Author(s):  
Xiaoping Luo ◽  
Li Ding ◽  
Jingxia Xu ◽  
Nasser Chegini
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Binding Protein ◽  
Muscle Cells ◽  
Time Dependent ◽  
Early Gene ◽  
A Cell

Altered expression of the TGF-β system is recognized to play a central role in various fibrotic disorders, including leiomyoma. In this study we performed microarray analysis to characterize the gene expression profile of leiomyoma and matched myometrial smooth muscle cells (LSMC and MSMC, respectively) in response to the time-dependent action of TGF-β and, after pretreatment with TGF-β type II receptor (TGF-βRII) antisense oligomer-blocking/reducing TGF-β autocrine/paracrine actions. Unsupervised and supervised assessments of the gene expression values with a false discovery rate selected at P ≤ 0.001 identified 310 genes as differentially expressed and regulated in LSMC and MSMC in a cell- and time-dependent manner by TGF-β. Pretreatment with TGF-βRII antisense resulted in changes in the expression of many of the 310 genes regulated by TGF-β, with 54 genes displaying a response to TGF-β treatment. Comparative analysis of the gene expression profile in TGF-βRII antisense- and GnRH analog-treated cells indicated that these treatments target the expression of 222 genes in a cell-specific manner. Gene ontology assigned these genes functions as cell cycle regulators, transcription factors, signal transducers, tissue turnover, and apoptosis. We validated the expression and TGF-β time-dependent regulation of IL-11, TGF-β-induced factor, TGF-β-inducible early gene response, early growth response 3, CITED2 (cAMP response element binding protein-binding protein/p300-interacting transactivator with ED-rich tail), Nur77, Runx1, Runx2, p27, p57, growth arrest-specific 1, and G protein-coupled receptor kinase 5 in LSMC and MSMC using real-time PCR. Together, the results provide the first comprehensive assessment of the LSMC and MSMC molecular environment targeted by autocrine/paracrine action of TGF-β, highlighting potential involvement of specific genes whose products may influence the outcome of leiomyoma growth and fibrotic characteristics by regulating inflammatory response, cell growth, apoptosis, and tissue remodeling.

scholarly journals Time-dependent changes in ARE-driven gene expression by use of a noise-filtering process for microarray data

2002 ◽  
Vol 9 (3) ◽  
pp. 137-144 ◽  
Author(s):  
Jiang Li ◽  
Jeffrey A. Johnson
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Microarray Data ◽  
Transcriptional Activation ◽  
Expression Profiles ◽  
Time Dependent ◽  
Gene Clustering ◽  
Noise Filtering ◽  
Human Neuroblastoma ◽  
Rank Analysis

The current study was designed to identify the time-dependent gene expression profiles of antioxidant responsive element (ARE)-driven genes induced by tert-butylhydroquinone (tBHQ). A set of simple noise-filtering methods was introduced to evaluate and minimize the variance of microarray datasets. Gene expression induced by tBHQ (10 μM) in IMR-32 human neuroblastoma cells was analyzed by means of large-scale oligonucleotide microarray. Rank analysis was used to determine the acceptable number of independent samples necessary to eliminate false positives from the dataset. A dramatic reduction in the number of genes passing the rank analysis was achieved by using a 3 × 3 matrix comparison. Reproducibility was evaluated based on the coefficient of variation for average difference change. Completion of these analyses revealed that 101 of the 9,670 genes examined showed dynamic changes with treatment ranging from 4 h to 48 h. Since certain ARE-driven genes have been already identified, gene clustering would presumably group them together based on similar regulation. Self-organizing map grouped the genes induced by tBHQ into 12 (4×3) distinct clusters. Those previously identified ARE-driven genes were shown to group into different clusters. Since all potential ARE-driven genes did not cluster together, we speculate that multiple transcription factors and/or multiple signal transduction pathways contribute to transcriptional activation of the ARE. In conclusion, many novel potential ARE-driven genes were identified in this study. They function in detoxification and antioxidant defense, neuronal proliferation and differentiation, and signal transduction. The noise-filtering process applied to these microarray data, therefore, has proven to be very useful in identification of the time-dependent changes in ARE-drive gene expression.

scholarly journals Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

2021 ◽  
Vol 9 (2) ◽  
pp. 255
Author(s):  
Angelo Iacobino ◽  
Giovanni Piccaro ◽  
Manuela Pardini ◽  
Lanfranco Fattorini ◽  
Federico Giannoni
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Physiological State ◽  
Transcriptional Response ◽  
Sos Response ◽  
Resistant Mutant ◽  
Time Dependent ◽  
Dependent Manner ◽  
Gyra Gene ◽  
Drug Concentrations

Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.

scholarly journals Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110198
Author(s):  
Mohammed S. Aldughaim ◽  
Mashael R. Al-Anazi ◽  
Marie Fe F. Bohol ◽  
Dilek Colak ◽  
Hani Alothaid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantum Dots ◽  
Cancer Cells ◽  
Cadmium Telluride ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dependent Manner ◽  
Cdte Qds ◽  
Cadmium Telluride Quantum Dots

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 μg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.

scholarly journals Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

2008 ◽  
Vol 3 ◽  
pp. BMI.S590 ◽  
Author(s):  
Han-Jin Park ◽  
Jung Hwa Oh ◽  
Seokjoo Yoon ◽  
S.V.S. Rana
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
General Purpose ◽  
Time Dependent ◽  
Expression Data ◽  
Benzene Exposure ◽  
Microarray Analyses ◽  
First Time ◽  
Affymetrix Gene Chip

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.

CFTR ΔF508 mutation has minimal effect on the gene expression profile of differentiated human airway epithelia

2005 ◽  
Vol 289 (4) ◽  
pp. L545-L553 ◽  
Author(s):  
Joseph Zabner ◽  
Todd E. Scheetz ◽  
Hakeem G. Almabrazi ◽  
Thomas L. Casavant ◽  
Jian Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Primary Cultures ◽  
Gene Expression Profiles ◽  
Filter Method ◽  
Tissue Destruction ◽  
Airway Epithelia

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel regulated by phosphorylation. Most of the disease-associated morbidity is the consequence of chronic lung infection with progressive tissue destruction. As an approach to investigate the cellular effects of CFTR mutations, we used large-scale microarray hybridization to contrast the gene expression profiles of well-differentiated primary cultures of human CF and non-CF airway epithelia grown under resting culture conditions. We surveyed the expression profiles for 10 non-CF and 10 ΔF508 homozygote samples. Of the 22,283 genes represented on the Affymetrix U133A GeneChip, we found evidence of significant changes in expression in 24 genes by two-sample t-test ( P < 0.00001). A second, three-filter method of comparative analysis found no significant differences between the groups. The levels of CFTR mRNA were comparable in both groups. There were no significant differences in the gene expression patterns between male and female CF specimens. There were 18 genes with significant increases and 6 genes with decreases in CF relative to non-CF samples. Although the function of many of the differentially expressed genes is unknown, one transcript that was elevated in CF, the KCl cotransporter (KCC4), is a candidate for further study. Overall, the results indicate that CFTR dysfunction has little direct impact on airway epithelial gene expression in samples grown under these conditions.

scholarly journals Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

2013 ◽  
Vol 20 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Katherine H. Restori ◽  
Mary J. Kennett ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Expression Profiles ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Pneumonia Severity ◽  
Content Type ◽  
Amyloid A

ABSTRACTVaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.

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