Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, F508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-F508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.
Specimen part, Cell line
View SamplesWe investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice.
Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.
Age, Specimen part
View SamplesLung disease causes most of the morbidity and mortality in cystic fibrosis (CF). However, understanding its pathogenesis has been hindered by lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with targeted CFTR genes. We now report that within months of birth, CF pigs spontaneously develop hallmark features of CF lung disease including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting an equal opportunity host defense defect. In humans, the temporal and/or causal relationships between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation, but were less often sterile than controls. Moreover, after intrapulmonary bacterial challenge, CF pigs failed to eradicate bacteria as effectively as wild- type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Finding that CF pigs have a bacterial host defense defect within hours of birth provides an exciting opportunity to further investigate pathogenesis and to test therapeutic and preventive strategies before secondary consequences develop.
Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesGerman landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Specimen part
View SamplesGerman landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn).
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Specimen part
View SamplesGerman landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesGerman landrace gilts were fed a low protein diet (LP, 6% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View SamplesGerman landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Specimen part
View Samples