Project description:We used microarrays to detail the gene expression profile during WAT -beige transition by treatment of beta adrenergic receptor agonist . Stromal vascular fractions (SVF) from mice (n = 3/group) that received vehicle or beta3 adrenergic receptor agonist, CL, treatment were served for RNA extraction and hybridization on Affymetrix microarrays. We are trying to find out angiogenic factors genes dynamics during white adipose tissues (WAT) - beige transition.
Project description:Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β<sub>2-</sub>adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β<sub>2</sub>-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β<sub>2</sub>-adrenergic receptors and the stimulatory G protein, G<sub>s</sub>. Unbiased transcriptomic and metabolomic analyses showed that chronic β<sub>2</sub>-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β<sub>2</sub>-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.
Project description:We used microarrays to detail the gene expression profile during WAT -beige transition by treatment of beta adrenergic receptor agonist .
Project description:Autonomic drive plays a pivotal role in cardiac regeneration. Sympathetic or cholinergic denervation impairs myocardial regrowth in neonatal mouse and zebrafish hearts. Here, we uncovered the mechanistic underpinning of adrenergic signaling in regenerative repair of the heart to be critically dependent on immunomodulation. Through pharmacological and genetic manipulations, we identified adrenergic receptor alpha-1 as a key regulator of macrophage phenotypic diversification following myocardial infarction in zebrafish. Single-cell transcriptomics revealed that the receptor signals activation of an ‘extracellular matrix remodeling’ transcriptional program characterized by upregulation of matrix proteins and matrix-modifying enzymes in a macrophage subset. Functionally, adrenergic receptor alpha-1-activated macrophages regulate fibrotic response of the heart by mediating collagenous extracellular matrix turnover and myofibroblast activation, allowing vascularization and cardiomyocyte cell cycle entry at the infarcted lesion. These findings not only unravel the mechanism of adrenergic signaling in macrophage phenotypic and functional determination, but also highlight the potential of neural modulation for regulation of fibrosis and coordination of myocardial regenerative response.
Project description:Analysis of the effects of 4 hr and 24 hr propranolol treatment on gene expression of SVR mouse angiosarcoma cells. The hypothesis tested in the present study was that inhibiton of beta adrenergic receptor signaling could ablate the oncogenic properties of angiosarcoma cells. Results provide important information of the response of angiosarcoma cells to ablated beta adrenergic receptor signaling. The total RNA was obtained from mouse angiosarcoma cells cultured in monolayer at 0, 4, and 24 hrs of 50 micromolar propranolol treatment. Illumina microarrays were performed to determine the whole genome expression changes following treatment.
Project description:Analysis of the effects of 4 hr and 24 hr propranolol treatment on gene expression of SVR mouse angiosarcoma cells. The hypothesis tested in the present study was that inhibiton of beta adrenergic receptor signaling could ablate the oncogenic properties of angiosarcoma cells. Results provide important information of the response of angiosarcoma cells to ablated beta adrenergic receptor signaling.
Project description:We screened RNAseq results from RAW 264.7 macrophages for previous empirically-defined M2 genes in the whole transcriptome that followed the Arg1 pattern of up-regulation by β-adrenergic-signaling with inhibition by Cebpb gene knockdown. We also screened RAW 264.7 macrophages for empirically-defined M1 genes that exhibited the orthogonal pattern of Arg1 regulation (i.e., down-regulation by β-adrenergic signaling, with rescue of this effect by Cebpb knockdown).