Manuscript Topics

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator, crucial in the regulation of cell survival, proliferation, suppression of apoptosis, migration, angiogenesis, lymphangiogenesis, and immune response. S1P content is strictly determined by the equilibrium between synthesis by sphingosine kinase, dephosphorylation to sphingosine by S1P phosphatases (SPP1 and SPP2) and irreversible degradation by S1P lyase. In many cell types S1P produced inside cells can be sevreted and outside the cell it can signal through five specific G protein-coupled receptors S1P1-5 (S1PR) in autocrine, paracrine, and/or endocrine manner. Cellular and temporal expression of these S1P specific receptors coupled to various monomeric G-proteins determine specific roles of SphK/S1P/S1PR axis in organ systems. Of interest, the export of S1P through specific poorly characterized transporters, allows to mammalian cells (i.e cancer cells) to affect the extracellular microenvironment. A deeper investigation of S1PR-mediated signals and of S1P transporters could be beneficial for extending our knowledge of cell homeostasis, tissue organ /regeneration and pathogenesis.

In the current special issue, we have attempted to summarize the most recent advances in the field of S1P, its generating and breaking down enzymes, its transporters and S1PR biology in order to provide novel insights into the complex signaling networks regulated by S1P in human homeostasis and diseases.

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