Involvement of urokinase-type plasminogen activator in sphingosylphosphorylcholine-induced angiogenesis.
Sphingosylphosphorylcholine (SPC) has been shown to accelerate wound healing. As angiogenesis is fundamental to proper wound healing, we examined the effect of SPC on angiogenesis using a well-established rat aortic ring assay. SPC significantly stimulated the sprouting of endothelial cells from rat aortic ring. Recognizing its potential effect on angiogenesis, we further investigated the action of SPC using human umbilical vein endothelial cells (HUVECs) cultured in vitro. SPC significantly accelerated the closure of in vitro wound. In addition, SPC markedly enhanced the chemotactic migration and capillary-like tube formation. Subsequently, we examined whether SPC affected the production of urokinase-type plasminogen activator (uPA), an important regulator of angiogenesis, and found that SPC stimulated the expression of uPA at both the transcriptional and translational levels. Consistent with these results, SPC increased the activity of cell-surface-associated plasminogen activator. Pretreatment with antiuPA antibody significantly diminished both the chemotactic migration and capillary-like tube formation, indicating the potential importance of uPA in SPC-induced angiogenesis. Together, these results suggest that SPC may affect angiogenesis in the wound-healing process via regulation of uPA production.
Piao
Yong-Jun
YJ
Department of Dermatology, School of Medicine, Chungnam National University, Daesa-dong, Daejeon, Korea.
Lee
Chang-Hi
CH
Zhu
Ming Ji
MJ
Kye
Kyung-Chae
KC
Kim
Jin-Man
JM
Seo
Young-Joon
YJ
Suhr
Ki-Beom
KB
Park
Jang-Kyu
JK
Kim
Chang Deok
CD
Lee
Jeung-Hoon
JH
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D014568:Urokinase-Type Plasminogen Activator; D013110:Sphingosine