Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA144589 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We show that knock-in mutations of the nuclear corepressor SMRT in C57Bl6 mice (SMRTmRID) produces a novel respiratory distress syndrome (RDS) due to prematurity of the type I pneumocyte. Treatment with the anti-thyroid hormone drug, propylthiouracil (PTU), completely rescues the SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which in turn appears to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify a second nuclear receptor, the TR, in type I pneumocyte differentiation and suggest a new type of therapeutic option in the treatment of glucocorticoid non-responsive RDS. Total RNA was obtained from WT and SMRT-RID E18.5 lungs of embryos from mothers treated with Diet containing 0.15% PTU or control chow for 2 days (from E16.5).
2011-10-13 | E-GEOD-30661 | biostudies-arrayexpress
Project description:We show that knock-in mutations of the nuclear corepressor SMRT in C57Bl6 mice (SMRTmRID) produces a novel respiratory distress syndrome (RDS) due to prematurity of the type I pneumocyte. Treatment with the anti-thyroid hormone drug, propylthiouracil (PTU), completely rescues the SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which in turn appears to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify a second nuclear receptor, the TR, in type I pneumocyte differentiation and suggest a new type of therapeutic option in the treatment of glucocorticoid non-responsive RDS.
2011-10-14 | GSE30661 | GEO
Project description:The disease caused by the novel coronavirus of 2019 (COVID-19) has resulted in significant morbidity and mortality world-wide. A systemic hyper-inflammation characterizes the severe COVID-19 disease often associated with acute respiratory distress syndrome (ARDS). Bloodbiomarkers with prognostic relevance are of great importance in effective triage and critical care of severe COVID-19 patients. In the present study we report higher plasma abundance of soluble urokinase-type plasminogen activator receptor (sUPAR), shown to be expressed by an abnormally expanded circulating myeloid cell population, in severe COVID-19 patients with acute respiratory distress syndrome. SUPAR level was found to be linked to a characteristic proteomic signature of plasma. A receiver operator characteristics curve analysis identified a cut-off value of sUPAR at 2000pg/ml, which was linked to characteristic differential expression in the immune transcriptome as well as clinical outcomes in our patient cohort. Thus we identified sUPAR as a biomarker with strong predictive potential for clinical outcomes in severe COVID-19.
2023-07-17 | PXD026510 | Pride
Project description:SMRT (silencing mediator of retinoid and thyroid hormone receptors) is recruited by numerous transcription factors to mediate lineage and signal dependent transcriptional repression. We generated a knock-in mutation in the receptor interaction domain (RID) of SMRT (SMRTmRID) that solely disrupts its interaction with nuclear hormone receptors. SMRTmRID-derived 3T3-MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. We measured global gene expression in wild-type versus SMRTmRID-derived 3T3-MEFs in the undifferentiated state to examine which pathways were altered. Our results demonstrate that SMRT-RID dependent repression is a key determinant of the adipogenic set point. Experiment Overall Design: 3T3 cells derived from wild-type and SMRT RID MEFs were cultured under pre-differentiated conditions prior to harvesting for RNA.
2009-01-18 | E-GEOD-13143 | biostudies-arrayexpress
Project description:SMRT (silencing mediator of retinoid and thyroid hormone receptors) is recruited by numerous transcription factors to mediate lineage and signal dependent transcriptional repression. We generated a knock-in mutation in the receptor interaction domain (RID) of SMRT (SMRTmRID) that solely disrupts its interaction with nuclear hormone receptors. SMRTmRID-derived 3T3-MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. We measured global gene expression in wild-type versus SMRTmRID-derived 3T3-MEFs in the undifferentiated state to examine which pathways were altered. Our results demonstrate that SMRT-RID dependent repression is a key determinant of the adipogenic set point. Keywords: SMRTmRID expression compared to wild-type
2009-01-07 | GSE13143 | GEO
Project description:The Acute Respiratory Distress Syndrome (ARDS)/Acute Lung Injury (ALI) was described 30 years ago, yet the interaction between specific sets of genes involved in this syndrome remains incompletely understood. Keywords: disease state analysis
2008-02-15 | GSE10474 | GEO
Project description:Proteomic investigation of immune response of Lung Tissue from Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Tree Shrews
2023-05-17 | PXD042280 |
Project description:Pulmonary surfactant (PS) produced by alveolar type II (ATII) cells is necessary in maintaining normal lung function, and a decrease or change in composition of PS is the main cause of alveolar collapse in acute respiratory distress syndrome (ARDS). But the mechanism of decrease or com-position change of PS is still unknown.
2023-09-06 | GSE226486 | GEO
Project description:The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoR∆ID) that cannot interact with the TR. L-NCoR∆ID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoR∆ID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoR∆ID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3. Keywords: NCoR, thyroid hormone signaling, mouse liver, DNA Microarray To better assess the role of NCoR in positive and negative regulation we performed micorarray analysis of gene expression in the livers of euthyroid and hypothyroid control and L-NCoR∆ID mice.
2008-12-03 | E-GEOD-10001 | biostudies-arrayexpress