Pulmonary Hypertension (PH) is a frequent complication of Pulmonary Fibrosis (PF). PH can be seen in PF in the abscence of hypoxemia, irrespective of the degree of fibrosis. At the same time, a consistent number of patients with advanced PF never develop PH. The pathogenesis of PH secondary to PF remains unclear. PF patients are often referred to lung transplantation, but they present a higher incidence of pimary graft dysfunction than other diseases. The cause of this is unknown, and the relationship with PH remains unclear.
Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis.
Specimen part, Disease, Disease stage
View SamplesAlthough multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.
De novo synthesize of bile acids in pulmonary arterial hypertension lung.
Specimen part
View SamplesProduction 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing.
Specimen part
View SamplesPMK-1 is involved in the heat stress response of C. elegans, translocates to the nucleus upon heat exposure and influences the expression of chaperone genes, proteasomal subunits and protein-biosynthesis related genes. Overall design: Differential Gene expression of WT and pmk-1 deletion mutant (KU25) after 5 hours at 35°C
The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans.
Cell line, Subject
View SamplesMicroarray analysis obtained from RNA of AML12 cells stably expresing Zfp125 or empty vector (EV)
The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia.
Specimen part, Cell line
View SamplesWe used microarrays to analyze the global expression patterns for 22 commercially available pancreatic cancer cell lines
Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems.
Specimen part, Cell line
View SamplesHow organ size and form are controlled during development is a major question of biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here we report that non-nutritional signals from blood vessels surprisingly act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
Blood vessels restrain pancreas branching, differentiation and growth.
Specimen part
View SamplesTGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments.
Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems.
Specimen part, Cell line, Treatment
View SamplesTime Course of TGF-beta treatment of A549 lung adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments.
ConceptGen: a gene set enrichment and gene set relation mapping tool.
Cell line
View Samples