Abstract
BackgroundSerotonin (5-HT) is a biogenic amine that also acts as a mitogen and a developmental signal early in rodent embryogenesis. Genetic and pharmacological disruption of 5-HT signaling causes various diseases and disorders via mediating central nervous system, cardiovascular system, and serious abnormalities on a growing embryo. Today, neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet.Methodology/Principal FindingsIn an attempt to identify the genes altered by 5-HT signaling pathways, we analyzed the global gene expression via the Illumina array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281 probe sets representing 30,854 genes in megakaryocytes isolated from mice infused with 5-HT or saline. We identified 723 differentially expressed genes of which 706 were induced and 17 were repressed by elevated plasma 5-HT.Conclusions/SignificanceHierarchical gene clustering analysis was utilized to represent relations between groups and clusters. Using gene ontology mining tools and canonical pathway analyses, we identified multiple biological pathways that are regulated by 5-HT: (i) cytoskeletal remodeling, (ii) G-protein signaling, (iii) vesicular transport, and (iv) apoptosis and survival. Our data encompass the first extensive genome-wide based profiling in the progenitors of platelets in response to 5-HT elevation in vivo.
Highlights
Serotonin (5-HT, 5-hydroxytryptamine) is a multifunctional signaling molecule that acts differently in different organ-systems, in a concentration-dependent manner. 5-HT plays roles, in adult life, but in development as well [1,2,3,4,5,6,7,8]
5-HT acts in various ways as a paracrine signaling molecule and as an enteric neurotransmitter that initiates peristaltic and secretory reflexes and acts as a hormone released from the small intestine that regulates bone formation and exerts effects on glucose and lipid metabolism [5]. 5-HT interacts with innate and acquired immunoeffector cells to promote defensive or pathophysiological inflammation and within the enteric nervous system 5-HT is neuroprotective and enhances neurogenesis, effectively protecting neurons from the detrimental effects of inflammation [3]
Murine models of 5-HT infusion At the end of 24-hour of mini pump insertion, platelets were counted in blood samples from both models, saline and 5-HTinfused mice and indicated that 5-HT infusion did not change the number of circulating platelets
Summary
Serotonin (5-HT, 5-hydroxytryptamine) is a multifunctional signaling molecule that acts differently in different organ-systems, in a concentration-dependent manner. 5-HT plays roles, in adult life, but in development as well [1,2,3,4,5,6,7,8]. 5-HT interacts with innate and acquired immunoeffector cells to promote defensive or pathophysiological inflammation and within the enteric nervous system 5-HT is neuroprotective and enhances neurogenesis, effectively protecting neurons from the detrimental effects of inflammation [3]. During early embryogenesis 5-HT is a mitogen and plays a crucial modulator role in the function and dysfunction of the serotonergic system [6,7,8,9] via modulating cell division, neuronal migration, cell differentiation, and synaptogenesis through activating 5-HT receptors and downstream signal transduction pathways [6,7,8,9]. Serotonin (5-HT) is a biogenic amine that acts as a mitogen and a developmental signal early in rodent embryogenesis. Neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet
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