Signal Transduction and Gene Regulation in the Endothelium
- 6 June 2022
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Perspectives in Medicine
- Vol. 13 (1), a041153
- https://doi.org/10.1101/cshperspect.a041153
Abstract
Extracellular signals act on G-protein-coupled receptors (GPCRs) to regulate homeostasis and adapt to stress. This involves rapid intracellular post-translational responses and long-lasting gene-expression changes that ultimately determine cellular phenotype and fate changes. The lipid mediator sphingosine 1-phosphate (S1P) and its receptors (S1PRs) are examples of well-studied GPCR signaling axis essential for vascular development, homeostasis, and diseases. The biochemical cascades involved in rapid S1P signaling are well understood. However, gene-expression regulation by S1PRs are less understood. In this review, we focus our attention to how S1PRs regulate nuclear chromatin changes and gene transcription to modulate vascular and lymphatic endothelial phenotypic changes during embryonic development and adult homeostasis. Because S1PR-targeted drugs approved for use in the treatment of autoimmune diseases cause substantial vascular-related adverse events, these findings are critical not only for general understanding of stimulus-evoked gene regulation in the vascular endothelium, but also for therapeutic development of drugs for autoimmune and perhaps vascular diseases.Keywords
This publication has 194 references indexed in Scilit:
- Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesisProceedings of the National Academy of Sciences of the United States of America, 2013
- Sphingosine Phosphate Lyase Regulates Murine Embryonic Stem Cell Proliferation and Pluripotency through an S1P2/STAT3 Signaling PathwayBiomolecules, 2013
- Regulation of Mammalian Physiology, Development, and Disease by the Sphingosine 1-Phosphate and Lysophosphatidic Acid ReceptorsChemical Reviews, 2011
- Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus InfectionCell, 2011
- Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein MProceedings of the National Academy of Sciences of the United States of America, 2011
- FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous systemBritish Journal of Pharmacology, 2009
- Mechanotransduction in vascular physiology and atherogenesisNature Reviews Molecular Cell Biology, 2009
- Up-regulating Sphingosine 1-Phosphate Receptor-2 Signaling Impairs Chemotactic, Wound-healing, and Morphogenetic Responses in Senescent Endothelial CellsOnline Journal of Public Health Informatics, 2008
- The vascular S1P gradient—Cellular sources and biological significanceBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2008
- Asymmetric Synthesis of Conformationally Constrained Fingolimod Analogues—Discovery of an Orally Active Sphingosine 1-Phosphate Receptor Type-1 Agonist and Receptor Type-3 AntagonistJournal of Medicinal Chemistry, 2007