Disease relevance of Edg3

• Using receptor-null mice, we show that S1P, acting on S1P3 receptor expressed on both type I and type II alveolar epithelial cells but not vascular endothelium, induces pulmonary edema by acute tight junction opening [1].
• Because S1P3-null mice are resistant to S1P-induced pulmonary leakage, either alone or in the presence of TNF, S1P3 antagonism may be useful in protecting epithelial integrity in pulmonary disease [1].
• S1P3-/- bone marrow-derived mononuclear cells (BMCs) failed to augment neovascularization after hind limb ischemia [2].

High impact information on Edg3

• The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization [3].
• HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3 [4].
• S1P, acting through S1P3, regulates epithelial integrity and acts additively with TNF in compromising respiratory barrier function [1].
• S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF [1].
• Immunomodulator FTY720 Induces Myofibroblast Differentiation via the Lysophospholipid Receptor S1P3 and Smad3 Signaling [5].

Biological context of Edg3

• Thus, Edg-3, whose mRNA expression is downregulated during cell differentiation, may be responsible for the S1P-induced Ca2+ response in HL-60 leukemia cells [6].
• Mature DC, but not immature in vitro differentiated DC, were found to migrate to S1P, a phenomenon that correlated to the up-regulation of S1P1 and S1P3 in maturing DC [7].
• Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate [8].

Anatomical context of Edg3

• We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells [9].
• Furthermore, they suggest that SPP-induced I(K.ACh) activation in human atrial myocytes is mediated by the Edg-3 subtype of SPP receptors [10].
• Of these putative receptors, Edg-3 mRNA was abundantly expressed in undifferentiated HL-60 cells [6].
• Likewise, recovery of blood flow was dramatically reduced after induction of hindlimb ischemia in mice deficient for the S1P receptor 3 (S1P3) [2].
• Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor [2].

Associations of Edg3 with chemical compounds

• The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis [11].
• Moreover, activation of I(K.ACh) by SPP was blocked by the Edg-3-selective antagonist suramin, which did not affect basal or carbachol-stimulated K(+) currents [10].
• Involvement of EdgRs was tested with suramin (specific inhibitor of Edg-3) [12].

Other interactions of Edg3

• Indeed, in differentiated cells a significant increase of EDG3/S1P3 together with a large decrease of EDG5/S1P2 expression at mRNA as well as protein level was detected [13].

Analytical, diagnostic and therapeutic context of Edg3

• WT but not S1P3-null mice showed disruption of pulmonary epithelial tight junctions and the appearance of paracellular gaps between epithelial cells by electron microscopy within 1 h of airways exposure to S1P [1].
• High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor [14].

References