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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/G(i)/PLC/Ca2+ signaling pathways

Cited 37 times inthomson ciCited 34 times inthomson ci
Title
Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/G(i)/PLC/Ca2+ signaling pathways
Author
Yoon, Chang MinHong, Bok SilMoon, Hyung GeunLim, SeyoungSuh, Pann-GhillKim, Yoon-KeunChae, Chi-BomGho, Yong Song
Keywords
NDOTHELIAL-CELL MIGRATION; LYMPHATIC VESSEL FORMATION; PROTEIN-COUPLED RECEPTORS; GROWTH-FACTOR; VEGF-C; LYSOPHOSPHATIDIC ACID; EXTRACELLULAR EXPORT; VASCULAR MATURATION; ADHESION MOLECULE-1; NITRIC-OXIDE
Issue Date
200808
Publisher
AMER SOC HEMATOLOGY
Citation
BLOOD, v.112, no.4, pp.1129 - 1138
Abstract
The lymphatic system plays pivotal roles in mediating tissue fluid homeostasis and immunity, and excessive lymphatic vessel formation is implicated in many pathological conditions, which include inflammation and tumor metastasis. However, the molecular mechanisms that regulate lymphatic vessel formation remain poorly characterized. Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that is implicated in a variety of biologic processes such as inflammatory responses and angiogenesis. Here, we first report that S1P acts as a lymphangiogenic mediator. S1P induced migration, capillarylike tube formation, and intracellular Ca2+ mobilization, but not proliferation, in human lymphatic endothelial cells (HLECs) in vitro. Moreover, a Matrigel plug assay demonstrated that S1P promoted the outgrowth of new lymphatic vessels in vivo. HLECs expressed S1P1 and S1P3, and both RNA interference-mediated down-regulation of S1P1 and an S1P1 antagonist significantly blocked S1P-mediated lymphangiogenesis. Furthermore, pertussis toxin, U73122, and BAPTA-AM efficiently blocked SIP-induced in vitro lymphangiogenesis and intracellular Ca2+ mobilization of HLECs, indicating that S1P promotes lymphangiogenesis by stimulating S1P1/Gi/phospholipase C/Ca2+ signaling pathways. Our results suggest that S1P is the first lymphangiogenic bioactive lipid to be identified, and that S1P and its receptors might serve as new therapeutic targets against inflammatory diseases and lymphatic metastasis in tumors.
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DOI
http://dx.doi.org/10.1182/blood-2007-11-125203
ISSN
0006-4971
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