TGF is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGF mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGF in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGF in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGF, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.
miR-29 is a major regulator of genes associated with pulmonary fibrosis.
Specimen part, Cell line
View SamplesAffymetrix human whole transcriptome array (HTA 2.0) completed on patients with Crohn's disease undergoing their first ileocolic resection
Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.
Specimen part
View SamplesIRAK4 kinase plays a critical role in innate immune responses and inflammation by modulating the TLR/IL-1R signaling pathway, yet the mechanism by which it regulates downstream pathways and transcription factors to induce inflammatory cytokines is unclear. IRAK4 can mediate signaling events by mechanisms both dependent and independent of its kinase activity. Understanding this regulation is important for deciphering the role of IRAK4 and for the development of treatments for inflammatory diseases and cancer. Through transcriptomic and biochemical analyses of primary human monocytes treated with a highly potent and selective inhibitor of IRAK4, we show that IRAK4 kinase activity controls the transcription factor IRF5 which in turn induces inflammatory cytokine and type I interferon transcription in myeloid cells. We also show that IRAK4 kinase activity does not control activation of NF-B. Following TLR stimulation, translocation of IRF5, but not NF-B, to the nucleus in human monocytes is abolished by IRAK4 kinase inhibition. In addition, binding of IRF5, but not NF-B p65, to promoters of inflammatory target genes (TNF- and IP10) is blocked with an IRAK4 kinase inhibitor. IKK, a known activator of IRF5, is phosphorylated in response to TLR mediated signaling, and inhibition of IRAK4 kinase blocks IKK phosphorylation. Pharmacological inhibition of IKK and TAK1, the upstream kinase of IKK, in human monocytes blocks IL-1, IL-6 and TNF- cytokine production, as well as IRF5 translocation to the nucleus. Taken together, our data suggest a novel mechanism by which IRAK4 kinase activity regulates TAK1 and IKK activation, leading to the translocation of IRF5 and induction of inflammatory cytokines in human monocytes.
IRAK4 kinase activity controls Toll-like receptor-induced inflammation through the transcription factor IRF5 in primary human monocytes.
Treatment
View SamplesOverexpression of a grapevine C-repeat binding factor (CBF) gene, VvCBF4 in cv. Freedom was found to improve freezing survival in non-cold-acclimated vines.
The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape.
Specimen part
View SamplesAfter ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these four cell types. Analysis of the RNA present in each bovine cell type using Affymetrix microarrays yielded new cell-specific genetic markers, functional insight into the behavior of each cell type via Gene Ontology Annotations and Ingenuity Pathway Analysis, and evidence of small and large luteal cell lineages using Principle Component Analysis. Enriched expression of select genes for each cell type was validated by qPCR. This expression analysis offers insight into the lineage and differentiation process that transforms somatic follicular cells into luteal cells.
Gene expression profiling of bovine ovarian follicular and luteal cells provides insight into cellular identities and functions.
No sample metadata fields
View SamplesPotted Cabernet Sauvignon vines in the greenhouse were exposed to irrigated controls, non-irrigated water-deficits, and saline treatments for 16 days. Plant shoot tips were harvested every 4 days (0,4,8,12, and 16 days) to measure the progression of changes of global gene expression due to the stress.
Water and salinity stress in grapevines: early and late changes in transcript and metabolite profiles.
Specimen part
View SamplesThis series regroups different datasets (training set, test set, validation set, longitudinal set, separated cell set) to identify and characterise a specific transcriptional signature for patients with active TB, distinct from patients with latent TB and healthy controls. The training set dataset was used to identify a whole blood transcriptional signature for active TB patients in London, across a range of ethnicity. This signature was then validated in an independent cohort of patients, also recruited in London (the test set), and then further confirmed in an additional independent cohort recruited in Cape Town, South Africa (validation set), in order to confirm that the defined signature was present in both high (Cape Town, South Africa) and medium incidence regions (London, UK). The longitudinal dataset was then used to explore how successful TB treatment modifies this transcriptional signature. The separated cell set compares the transcriptional profiles in purified cell subsets (neutrophils, monocytes and T cells) to assess which cell types are contributing to the whole blood signature, and in what way. These studies may ultimately help to improve the diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 weeks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques such as bronchoalveolar lavage (BAL). In some cases (30%) the bacill cannot be grown from sputum or BAL. Any diagnostic tool would need to be valid across a range of ethnicities, and be valid in both high and low incidence countries. A further aim was to determine whether latent TB patients have a distinct homogeneous or heterogeneous signature, since it is not currently possible to determine using present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria have been cleared, are still present but are controlled by an active immune response, or to predict which patients will develop active TB. Defining heterogeneity in the latent TB patients would be an important step in developing diagnostics which could detect those most at risk of developing active TB, and thus enable targeted preventive therapy. The latter situation may be determined if Latent patients have a blood transcriptional signature similar to that in Active patients. The transcriptional signature in whole blood and cell subsets from Active TB patients may also provide information as to the factors leading to immunopathogenesis, thus possibly identifying therapeutic targets. The transcriptional profile in latent TB may give information regarding protective factors controlling the infection, important for vaccine development. Finally, definition of a transcriptional signature which responds to therapy could facilitate the development of surrogate biomarkers for drug or vaccine studies.
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sex, Age, Race
View SamplesTuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. The goals of this study include: 1. Identify a transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment; 2. Identify a specific transcript signature that discriminated active TB from other inflammatory and infectious diseases; 3. Classify TB signature using modular and pathway analysis tools.
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sex, Age, Race
View SamplesThis dataset aims to validate and confirm the signature identified in the training set. The aim of the experiment was to define transcriptional signatures in whole blood of TB patients (before drug treatment) and healthy controls to distinguish the signature of Latent and Active TB patients from each other and from healthy controls. This will help in diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 wks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL. Secondly the aim was to determine whether Latent patients have a homogeneous or heterogeneous signature, one may expect the latter since it is not possible to determine by the present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria has been cleared, is still present but is controlled, or if patients are recently infected or reactivated and will develop active TB.
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sex, Age, Race
View SamplesThe aim of this study was to compare the transcriptional response to TB in regions of different incidence / prevalence.
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sex, Age, Race
View Samples