This SuperSeries is composed of the SubSeries listed below.
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesRationale: Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease by whole-lung transcriptome analysis. Methods: Wildtype mice were experimentally exposed to S. mansoni ova by intraperitoneal sensitization followed by tail vein augmentation, and the phenotype assessed by right ventricular catheterization and tissue histology, RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, the latter analyzed using 2 bioinformatic methods. Functional testing of the candidate IL-6 pathway was determined using IL6-knockout mice and the STAT3 inhibitor STI-201. Results: Wild-type mice exposed to S. mansoni had increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole lung transcriptome analysis identified the IL6-STAT3-NFATc2 pathway as being upregulated, which was confirmed by PCR and immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL6 or treated with STI-201 developed pulmonary hypertension associated with significant intima remodeling after exposure to S. mansoni. Conclusions: Whole lung transcriptome analysis identified upregulation of the IL6-STAT3-NFATc2 pathway, and IL6 signaling was found to be protective against Schistosoma-induced intimal remodeling.
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesThe study aimed to uncover differential expression pattern of regulatory microRNAs in bovine granulosa cells derived from preovulatory dominant and subordinate follicles. Overall design: We used ovarian follicle samples of experimental heifers slaughtered at day 19 of the estrous cycle . Follicles were catagorized as preovulatory dominant follicles (PDF) and anovulatory subordinate follicles (SF). The granulosa cells were collected from each follicle and subjected to microRNA enriched total RNA isolation and used for miRNAs deep sequencing. A total of 6 samples (three biological replicated from PDF and 3 biological replicates from SF) were used for miRNA deep sequencing.
MicroRNA Expression Profile in Bovine Granulosa Cells of Preovulatory Dominant and Subordinate Follicles during the Late Follicular Phase of the Estrous Cycle.
Subject
View SamplesAbsent in Melanoma 2 (AIM2) is a member of the HIN-200 family of hematopoietic, IFN-inducible nuclear proteins associated with infection defense and tumor pathology. Recently, AIM2 was found to act as a DNA sensor in innate immunity. In addition, a high frequency of AIM2-alterations was observed in microsatellite unstable tumors. To elucidate AIM2 function in colorectal tumors, we here addressed AIM2-responsive genes by microarray. Among genes up-regulated by AIM2, there were a number of interferon-stimulated genes (ISGs: IFIT1, IFIT2, IFIT3, IFI6, IRF7, ISG15, HLA-DRA, HLA-DRB, TLR3 and CIITA) as well as genes involved in intercellular adhesion and matrix remodeling. Expression of ISGs correlated with expression of AIM2 in ten different IFN- treated colorectal cancer cell lines. Moreover, knock-down of AIM2 resulted in reduced expression of HLA-DRA, HLA-DRB, and CIITA in IFN- treated cells. IFN- independent induction of HLA-DR genes and their encoded proteins was also demonstrated upon transient induction of AIM2. STAT-signaling was not involved in IFN- independent induction of ISGs, arguing against participation of cytokines released in an autocrine manner. Our data indicate that AIM2 mediates IFN- dependent and independent induction of several Interferon stimulated genes (ISGs) including genes encoding the MHC II antigens HLA-DR and .
Absent in Melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers.
Cell line
View SamplesSo far, the majority of research on piRNAs was carried out in popular model organisms such as fruit fly and mouse, which however do not closely reflect human PIWI biology. Thus, we high-throughput sequenced and computationally analyzed piRNAs expressed in the adult testis of the pig owing to its full set of mammalian Piwi paralogs, availability for repeat experiments and the existence of elementary data from previous studies on the porcine PIWI/piRNA system. We provide an exhaustive characterization of porcine piRNAs and genomic piRNA clusters. In addition, we reveal that a considerable proportion of piRNAs matches protein coding genes, exhibiting characteristics that point to a biogenesis within the post-transcriptional silencing mechanism of the PIWI/piRNA pathway, commonly referred to as ping pong cycle. We further show that the majority of identified piRNA clusters spans exonic sequences of protein-coding genes or pseudogenes, which indicates the existence of different mechanisms for the generation of piRNAs directed against mRNA. Our data provides evidence that spliced mRNAs, derived from such loci, are not only targeted by piRNAs but are also subject to ping pong cycle processing. Finally, we demonstrate that homologous genes are targeted by piRNAs in pig, mouse and human. Altogether, this strongly suggests a role for mammalian piRNA clusters in gene regulation alongside of TE repression.
piRNAs from Pig Testis Provide Evidence for a Conserved Role of the Piwi Pathway in Post-Transcriptional Gene Regulation in Mammals.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Treatment, Time
View SamplesAnalysis of ALR-deficient cells indicates that ALRs are not required for the IFN response to intracellular DNA. To explore whether AIM2-like receptors activated another innate signaling pathway upon
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Treatment, Time
View SamplesMicroarray analysis and quantitative real-time PCR revealed that TB40E infection of DCs led to changes of the gene expression pattern. A variety of pro-inflammatory cytokines and chemokines (CXCL10, CXCL11, CCL5), TLR3 and genes whose products function downstream of the TLR3 signalling pathway (e.g. IFN-, IFN-) were significantly upregulated.
Toll-like receptor 3 has no critical role during early immune response of human monocyte-derived dendritic cells after infection with the human cytomegalovirus strain TB40E.
Specimen part
View SamplesALS is a uniformly fatal neurodegenerative disease in which motor neurons in the spinal cord and brain stem are selectively lost. Individual motor - groups of motor neurons innervating single muscles - show widely varying degrees of disease resistance: in the final stages of ALS, nearly all voluntary movement is lost but eye movement and eliminative and sexual functions remain relatively unimpaired. These functions are controlled by motor neurons of the oculomotor (III), trochlear (IV) and abducens (VI) nuclei in the midbrain and brainstem, and by Onufs nucleus in the lumbosacral spinal cord, respectively. Correspondingly, in ALS autopsies the oculomotor and Onufs nuclei are almost completely preserved. We used microarray profiling of isolated wildtype mouse motor neurons to identify genes whose expression was characteristic of both oculomotor and Onufs nuclei but not of vulnerable lumbar spinal neurons, or vice versa.
Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration.
Sex, Specimen part
View SamplesUpstream of N-ras (UNR) is a conserved RNA-binding protein that regulates mRNA translation and stability by binding to sites generally located in untranslated regions (UTRs). In Drosophila, sex-specific binding of UNR to msl2 mRNA and the non-coding RNA roX plays key roles in the control of X-chromosome dosage compensation in both sexes. In order to investigate broader sex-specific functions of UNR, we have identified its RNA targets in adult male and female flies by high-throughput RNA binding and transcriptome analysis. Here we show that UNR binds to a large set of protein-coding transcripts and to a smaller set of non-coding RNAs in a sex-specific fashion. Overall design: Two replicates of UNR IP were performed in D.melanogaster adult males and females, and enrichment in either sex was compared with IgG IP as control. To correlate sex-specific UNR binding with sex-specific transcription and splicing we performed RNA-Seq experiments in males and females.
Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR.
Specimen part, Subject
View Samples