Project description:Neutrophils play a pivotal role in the pathogenesis of lung ischemia-reperfusion injury. The effect of pro-resolving lipid mediators, such as Resolvin D1, on early neutrophil trafficking has not been assessed in organ transplantation. We obtained single-cell RNA sequencing of leukocytes from syngeneic left lung grafts to elucidate the genetic changes induced by recipient treatment with Resolvin D1 or vehicle.
Project description:Adenosine 5’ monophosphate-activated protein kinase regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 mitogen-activated protein kinase.
Project description:Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38α in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion and transcription. Several previously unknown p38 target genes were found. Using gel mobility shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene expression profile by histological analysis and echocardiographic measurements, which indicated that p38 MAPK overexpression induced gene expression results in cell proliferation, myocardial inflammation and fibrosis. In conclusion, we defined the novel target genes and transcription factors as well as the functional effects of p38 MAPK in the heart. Expression profiling of p38 MAPK overexpression identified cell cycle regulatory and inflammatory genes critical for pathological processes in the adult heart. Experiment Overall Design: Left ventricular gene expression profiles three days after MKK3bE + WT p38α gene transfer were compared with those of Lac Z âtreated animals by screening Affymetrix Rat Expression Set 230_2.0 Arrays (there are 5 samples in both group).
Project description:Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38α in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion and transcription. Several previously unknown p38 target genes were found. Using gel mobility shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene expression profile by histological analysis and echocardiographic measurements, which indicated that p38 MAPK overexpression induced gene expression results in cell proliferation, myocardial inflammation and fibrosis. In conclusion, we defined the novel target genes and transcription factors as well as the functional effects of p38 MAPK in the heart. Expression profiling of p38 MAPK overexpression identified cell cycle regulatory and inflammatory genes critical for pathological processes in the adult heart. Keywords: Gene transfer
Project description:Activation of the innate immune system leading to a persistent state of low-grade of tissue inflammation greatly influences the risk of developing metabolic complications associated with obesity. In this study, we characterized the inflammatory state in adipose tissue from obese patients and explored the potential of the specialized pro-resolving mediator (SPM) resolvin D1 (RvD1) to actively terminate inflammation and promote its resolution. By means of high-troughput transcritomic analysis we identified a cytokine-related molecular signature in obese omental adipose tissue, characterized by a remarkable overexpression of interleukin (IL)-6, IL-1β and IL-10 associated with a concomitant increase in macrophage infiltration, which gradually increased in a body mass index-dependent manner. RNA profiling was conducted in 4 patients with morbid obesity and 4 control subjects using the Affymetrix Human Genome U219 expression array plate containing more than 36,000 transcripts and variants (Affymetrix, Inc., Santa Clara, CA).
Project description:Activation of the innate immune system leading to a persistent state of low-grade of tissue inflammation greatly influences the risk of developing metabolic complications associated with obesity. In this study, we characterized the inflammatory state in adipose tissue from obese patients and explored the potential of the specialized pro-resolving mediator (SPM) resolvin D1 (RvD1) to actively terminate inflammation and promote its resolution. By means of high-troughput transcritomic analysis we identified a cytokine-related molecular signature in obese omental adipose tissue, characterized by a remarkable overexpression of interleukin (IL)-6, IL-1β and IL-10 associated with a concomitant increase in macrophage infiltration, which gradually increased in a body mass index-dependent manner.
