Cholesterol is an essential cell membrane component and precursor in metabolic pathways. Control of cholesterol levels is essential to human health. The endocrine hormone FGF19 potently inhibits CYP7A1, which controls a key step in cholesterol catabolism. However, the molecular mechanisms that integrate FGF19 with other cholesterol metabolic pathways are incompletely understood. Here we show that FGF19 and analogue promote HDL biogenesis and cholesterol efflux from the liver by selectively modulating liver X receptor signaling without inducing hepatic steatosis. We further identify ATP-binding cassette transporter A1 and FGFR4 as mediators of this effect. In dyslipidemic Apoe-/- mice fed a Western diet, treatment with FGF19 analogue dramatically reduced atherosclerotic lesion area in aortas. In healthy human volunteers, FGF19 analogue caused a placebo-adjusted increase in HDL cholesterol levels of 26% in seven days. These findings outline a regulatory role for FGF19 in cholesterol metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis.
Therapeutic FGF19 promotes HDL biogenesis and transhepatic cholesterol efflux to prevent atherosclerosis.
Specimen part, Treatment
View SamplesJNK3 deficiency leads to upregulation of growth factors such as Vegfa, Pdgfb, Pgf, Hbegf and Tgfb3 in ischemic muscle. In order to ascertain the molecular mechanisms responsible for the accelerated blood flow recovery in Mapk10-deficient mice, a micro-array analysis of gastrocnemius muscle from these mice was performed after HLI. We observed a significant up-regulation of several growth factors known to improve blood flow recovery in the Mapk10-/- muscle compared to WT
Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis.
Specimen part
View SamplesTNF-a is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNF-a activates MEK/ERK in chondrocytes; however the overall functional relevance of MEK/ERK to TNF-a-regulated gene expression in chondrocytes is unknown. Chondrocytes were treated with TNF-a with or without the MEK1/2 inhibitor U0126 for 24 h. Microarray analysis was used to identify genes regulated by TNF-a in a MEK1/2-dependent fashion.
Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFalpha-induced MEK/ERK signalling.
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View SamplesMicroarray analysis was used to show that in gingival fibroblasts essentially all TGFB1 responsive genes were blocked by TAK inhibition
5Z-7-Oxozeanol Inhibits the Effects of TGFβ1 on Human Gingival Fibroblasts.
Specimen part, Treatment
View SamplesMetzincins and related genes (MARGS) play important roles in ECM remodeling in fibrotic conditions.
Renal Fibrosis mRNA Classifier: Validation in Experimental Lithium-Induced Interstitial Fibrosis in the Rat Kidney.
Sex, Specimen part
View SamplesSco1 is a gene required for cytochrome c oxidase biogenesis and the regulation of copper homeostasis. We characterized the transcriptional changes that occur as a result of liver-specific deletion of Sco1 in mice at 27 days of age
The Mitochondrial Metallochaperone SCO1 Is Required to Sustain Expression of the High-Affinity Copper Transporter CTR1 and Preserve Copper Homeostasis.
Age, Specimen part
View SamplesEndothelin-1 (ET-1) plays a critical role in connective tissue remodeling by fibroblasts during tissue repair and fibrosis. We investigated the molecular pathways in the transmission of ET-1 signals that lead to features of connective tissue remodeling, in particular the role of FAK (focal adhesion kinase).
Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation.
Specimen part, Treatment
View SamplesThis data provides evidence that elevation of cAMP levels has a dramatic effect on the transcriptome of yeast cells, with particular emphasis on mitochondrial function and the promotion of ROS production
cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation.
Treatment
View SamplesPlant respiration responses to elevated growth [CO2] are key uncertainties in predicting future crop and ecosystem function. In particular, the effects of elevated growth [CO2] on respiration over leaf development are poorly understood. This study tested the prediction that, due to greater whole-plant photoassimilate availability and growth, elevated [CO2] induces transcriptional reprogramming and a stimulation of nighttime respiration in leaf primordia, expanding leaves, and mature leaves of Arabidopsis thaliana. In primordia, elevated [CO2] altered transcript abundance, but not for genes encoding respiratory proteins. In expanding leaves, elevated [CO2] induced greater glucose content and transcript abundance for some respiratory genes, but did not alter respiratory CO2 efflux. In mature leaves, elevated [CO2] led to greater glucose, sucrose and starch content, plus greater transcript abundance for many components of the respiratory pathway, and greater respiratory CO2 efflux. Therefore, growth at elevated [CO2] stimulated dark respiration only after leaves transitioned from carbon sinks into carbon sources. This coincided with greater photoassimilate production by mature leaves under elevated [CO2] and peak respiratory transcriptional responses. It remains to be determined if biochemical and transcriptional responses to elevated [CO2] in primordial and expanding leaves are essential prerequisites for subsequent alterations of respiratory metabolism in mature leaves.
Developmental stage specificity of transcriptional, biochemical and CO2 efflux responses of leaf dark respiration to growth of Arabidopsis thaliana at elevated [CO2].
No sample metadata fields
View SamplesTranscriptional reprogramming and stimulation of leaf respiration by elevated CO2 concentration is diminished, but not eliminated, under limiting nitrogen supply.
Transcriptional reprogramming and stimulation of leaf respiration by elevated CO2 concentration is diminished, but not eliminated, under limiting nitrogen supply.
Age, Specimen part
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