Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA382975 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To identify putative novel specific targets of miR-199-5p, miR-199a-3p and miR-214-3p, we overexpressed these miRNAs in human MRC5 pulmonary fibroblasts (CCL-171) using synthetic pre-miRNAs or a synthetic “negative” pre-miRNA control (miR-Neg). RNA samples were harvested 48 hours post-transfection and 3 independent experiments were carried out.
2019-04-11 | GSE97824 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder characterized by fibroblast proliferation and the excess deposit of extracellular matrix proteins. The etiology of IPF is unknown, but a central role for microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been recently suggested. We report the upregulation of miR-199a-5p in mouse lungs undergoing bleomycin-induced fibrosis and also in human biopsies from IPF patients. Levels of miR-199a-5p were increased selectively in myofibroblasts and putative profibrotic effects of miR-199a-5p were further investigated in cultured lung fibroblasts. MiR-199a-5p expression was induced upon TGFβ exposure and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts. CAV1, a critical mediator of pulmonary fibrosis, was established as a bona fide target of miR-199a-5p. Finally, we also found an aberrant expression of miR-199a-5p in mouse models of kidney and liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. We propose miR-199a-5p as a major regulator of fibrosis that represents a potential therapeutic target to treat fibroproliferative diseases. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-01 | E-GEOD-34818 | biostudies-arrayexpress
Project description:To identify putative novel specific targets of mir-199-5p, we overexpressed miR-199a-5p as well as miR-21 and a siRNA targeted against CAV1 in human HFL1 pulmonary fibroblasts (CCL-153) by transfecting them with synthetic pre-miRNAs or a synthetic “negative” pre-miRNA as control (miR-Neg). RNA samples were harvested at 48 hours post-transfection and 2 independent experiments were carried out. Additional samples correspond to HFL1 cells treated or not with 10ng/ml TGFbeta for 48 hours in the absence of serum (2 independent experiments). 2 independent experiments performed in a one color design, corresponding to 7 conditions (miR-Neg, miR-199-5p, miR-21, si-Neg, si-CAV1, control, TGFbeta) and a total of 14 samples.
2013-02-01 | E-GEOD-34815 | biostudies-arrayexpress
Project description:Impact of miR-199-5p overexpression and CAV1 silencing on human lung fibroblasts
| PRJNA156287 | ENA
Project description:Whole transcriptome Identification of direct targets of miR-199a-5p and miR-424-3p using biotinylated pull-downs found that both miRNAs are likely to have a role in the cell cycle. HEK293T cells were transfected with biotinylated miRNAs (either miR-199a-5p or miR-424-3p). The miRNAs and target mRNA were pulled down with streptavidin and compared to the input control.
2013-12-02 | E-GEOD-40406 | biostudies-arrayexpress
Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
2024-01-26 | PXD042904 | Pride
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder characterized by fibroblast proliferation and the excess deposit of extracellular matrix proteins. The etiology of IPF is unknown, but a central role for microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been recently suggested. We report the upregulation of miR-199a-5p in mouse lungs undergoing bleomycin-induced fibrosis and also in human biopsies from IPF patients. Levels of miR-199a-5p were increased selectively in myofibroblasts and putative profibrotic effects of miR-199a-5p were further investigated in cultured lung fibroblasts. MiR-199a-5p expression was induced upon TGFβ exposure and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts. CAV1, a critical mediator of pulmonary fibrosis, was established as a bona fide target of miR-199a-5p. Finally, we also found an aberrant expression of miR-199a-5p in mouse models of kidney and liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. We propose miR-199a-5p as a major regulator of fibrosis that represents a potential therapeutic target to treat fibroproliferative diseases. This SuperSeries is composed of the SubSeries listed below.
2013-02-01 | GSE34818 | GEO
Project description:To assess the impact of miR-199a-5p silencing on lung fibrogenesis, LNA-miR-199a-5p (5mg/kg) or control formulated for in vivo delivery was instilled intratracheally 4 days and 2 days before intratracheal administration of bleomycin (1 unit/kg) or PBS as well as 4 days after bleomycin or PBS treatment.
2019-04-11 | GSE97825 | GEO
Project description:From a previous microarray study we developed a small chondrogenesis model. We performed qPCR and measured how knockdown of miR-199a-5p or miR-199b-5p could modulate chondrogenesis. Several experiments were used to determine the parameters of this model. We utilised parameter scan and manual sliding to refine the model. Within are two models - an initial model which only comprises of genes which we have data for, and an enhanced model which expands of the initial model to make more predictions - e.g. how miR-140-5p is indirectly regulated by miR-199a-5p and miR-199b-5p.
2023-06-06 | MODEL2305010001 | BioModels
Project description:To identify putative novel specific targets of mir-199-5p, we overexpressed miR-199a-5p as well as miR-21 and a siRNA targeted against CAV1 in human HFL1 pulmonary fibroblasts (CCL-153) by transfecting them with synthetic pre-miRNAs or a synthetic “negative” pre-miRNA as control (miR-Neg). RNA samples were harvested at 48 hours post-transfection and 2 independent experiments were carried out. Additional samples correspond to HFL1 cells treated or not with 10ng/ml TGFbeta for 48 hours in the absence of serum (2 independent experiments).
2013-02-01 | GSE34815 | GEO