Involvement of urokinase‐type plasminogen activator in sphingosylphosphorylcholine‐induced angiogenesis

Abstract:  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.

[1]  Jeung-Hoon Lee,et al.  Signaling events during induction of plasminogen activator inhibitor-1 expression by sphingosylphosphorylcholine in cultured human dermal fibroblasts. , 2004, The Journal of investigative dermatology.

[2]  G. Mills,et al.  Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. , 2003, Cancer research.

[3]  P. Higgins,et al.  Epithelial monolayer wounding stimulates binding of USF-1 to an E-box motif in the plasminogen activator inhibitor type 1 gene , 2002, Journal of Cell Science.

[4]  P. Mcglynn,et al.  Migration of vascular smooth muscle cells induced by sphingosine 1-phosphate and related lipids: potential role in the angiogenic response. , 2002, Experimental cell research.

[5]  L. Devy,et al.  The pro‐ or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  F. Castellino,et al.  Accelerated skin wound healing in plasminogen activator inhibitor-1-deficient mice. , 2001, The American journal of pathology.

[7]  K. Akassoglou,et al.  Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis. , 2001, American journal of physiology. Heart and circulatory physiology.

[8]  M. Pepper.  Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[9]  S. Chae,et al.  Sphingosine 1-Phosphate-induced Endothelial Cell Migration Requires the Expression of EDG-1 and EDG-3 Receptors and Rho-dependent Activation of αvβ3- and β1-containing Integrins* , 2001, The Journal of Biological Chemistry.

[10]  M. Detmar,et al.  Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4. , 2001, The Journal of clinical investigation.

[11]  T. Ohmori,et al.  Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells , 2000 .

[12]  J. Masferrer,et al.  Role of cyclooxygenases in angiogenesis. , 2000, Current medicinal chemistry.

[13]  M. Detmar,et al.  Thrombospondin‐1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice , 2000, The EMBO journal.

[14]  R. Tsuboi,et al.  Sphingosylphosphorylcholine stimulates contraction of fibroblast‐embedded collagen gel , 2000, The British journal of dermatology.

[15]  A. T. Kovala,et al.  Sphingosylphosphorylcholine induces endothelial cell migration and morphogenesis. , 2000, Biochemical and biophysical research communications.

[16]  P. Gerwins,et al.  Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. , 2000, Critical reviews in oncology/hematology.

[17]  Y. G. Kwon,et al.  Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. , 1999, Biochemical and biophysical research communications.

[18]  A. Luttun,et al.  Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure , 1999, Nature Medicine.

[19]  B. Gustavsson,et al.  Human endothelial cell migration is stimulated by urokinase plasminogen activator:plasminogen activator inhibitor 1 complex released from endometrial stromal cells stimulated with transforming growth factor beta1; possible mechanism for paracrine stimulation of endometrial angiogenesis. , 1998, Biology of reproduction.

[20]  K. Matsushita,et al.  Sphingosylphosphorylcholine stimulates proliferation and upregulates cell surface-associated plasminogen activator activity in cultured human keratinocytes. , 1998, The Journal of investigative dermatology.

[21]  S. Spiegel,et al.  A new wound healing agent--sphingosylphosphorylcholine. , 1996, The Journal of investigative dermatology.

[22]  H. Schnaper,et al.  Plasminogen activators augment endothelial cell organization in vitro by two distinct pathways , 1995, Journal of cellular physiology.

[23]  S. Milstien,et al.  Sphingolipid metabolites: Members of a new class of lipid second messengers , 1995, The Journal of Membrane Biology.

[24]  H. Schnaper,et al.  Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. , 1995, Circulation.

[25]  R. Nicosia,et al.  Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[26]  P. Jensen,et al.  Epidermal plasminogen activator is abnormal in cutaneous lesions. , 1988, The Journal of investigative dermatology.

[27]  L. Orci,et al.  Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells , 1987, The Journal of cell biology.

[28]  P. Jensen,et al.  Migrating keratinocytes express urokinase-type plasminogen activator. , 1987, The Journal of investigative dermatology.

[29]  A. Vaheri,et al.  Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells , 1987, The Journal of cell biology.

[30]  J. Emery,et al.  The Effect of Inhibition of Angiogenesis in Granulation Tissue on Wound Healing and the Fibroblast , 1985, Annals of plastic surgery.

[31]  T. Hla,et al.  Sphingosine 1-phosphate-induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of alpha vbeta3- and beta1-containing integrins. , 2001, The Journal of biological chemistry.

[32]  H. Dvorak,et al.  Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. , 1999, Current topics in microbiology and immunology.

[33]  Simon C Watkins,et al.  Impaired wound healing and angiogenesis in eNOS-deficient mice. , 1999, The American journal of physiology.

[34]  C. A. Demopoulos,et al.  The biological activity of acetylated sphingosylphosphorylcholine derivatives. , 1996, The international journal of biochemistry & cell biology.