title: Connective tissue growth factor (CTGF/CCN2) mediates angiogenic effect of S1P in human dermal microvascular endothelial cells.
abstract: OBJECTIVE
  The primary objective of this study was to examine the potential interaction between S1P, a pleiotropic lipid mediator, and CTGF/CCN2, a secreted multimodular protein, in the process of endothelial cell migration. The secondary objective was to determine whether C- and N-terminal domains of CTGF/CCN2 have a specific function in cell migration.
  
  
  METHODS
  Migration of HDMECs was examined in monolayer wound healing "scratch" assay, whereas capillary-like tube formation was examined in three-dimensional collagen co-culture assays.
  
  
  RESULTS
  We observed that S1P stimulates migration of HDMECs concomitant with upregulation of CTGF/CCN2 expression. Furthermore, the blockade of endogenous CTGF/CCN2 via siRNA abrogated S1P-induced HDMEC migration and capillary-like tube formation. Full-length CTGF induced cell migration and capillary-like tube formation with a potency similar to that of S1P, while C-terminal domain of CTGF was slightly less effective. However, N-terminal domain had only a residual activity in inducing capillary-like tube formation.
  
  
  CONCLUSIONS
  This study revealed that CTGF/CCN2 is required for the S1P-induced endothelial cell migration, which suggests that CTGF/CCN2 may be an important mediator of S1P-induced physiological and pathological angiogenesis. Moreover, this study shows that the pro-migratory activity of CTGF/CCN2 is located in the C-terminal domain.
authors.affiliation: Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. markiewi@musc.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: Markiewicz
authors.forename: Sashidhar S
authors.initials: SS
authors.lastname: Nakerakanti
authors.forename: Bagrat
authors.initials: B
authors.lastname: Kapanadze
authors.forename: Angela
authors.initials: A
authors.lastname: Ghatnekar
authors.forename: Maria
authors.initials: M
authors.lastname: Trojanowska
mesh_terms: D002465:Cell Movement; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D017434:Protein Structure, Tertiary; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: C526317:CCN2 protein, human; D008246:Lysophospholipids; D055513:Connective Tissue Growth Factor; C060506:sphingosine 1-phosphate; D013110:Sphingosine