title: Connective tissue growth factor induces tube formation and IL-8 production in first trimester human placental trophoblast cells.
abstract: OBJECTIVE
  To study the roles of connective tissue growth factor (CTGF) on tube formation (as a measure of cellular angiogenesis) and expression of angiogenesis-associated genes in first-trimester human extravillous trophoblast cells.
  
  
  METHODS
  The effects of recombinant human CTGF on tube forming ability were studied in the first trimester trophoblast cells using matrigel system. The expressions of genes involved in angiogenesis were studied using real time PCR microarray.
  
  
  RESULTS
  hCTGF (26nM) stimulated tube formation and enhanced tube length in these cells compared with control cells. However, hCTGF-stimulated tube formation was not inhibited by SU5416, a selective inhibitor of the membrane-bound tyrosine kinase activity of VEGF-2 receptor (Flk-1/KDR) indicating VEGF was not involved in the process. This was also supported by the observation that CTGF did not stimulate the expression of angiogenic factors VEGF or ANGPTL4 as determined by PCR array. To further elucidate roles of hCTGF in tube formation we then measured expression of several genes involved in angiogenesis signalling pathways. Among the genes, hCTGF increased expression of IL-8 mRNA by ∼6-fold and its protein secretion by ∼20-fold in these cells. Exogenously added IL-8 also stimulated the tube formation and proliferation in these cells.
  
  
  CONCLUSIONS
  hCTGF-induced tube formation is independent of VEGF. hCTGF stimulates production of IL-8, an important angiogenic factor in these cells. However their interrelationship in this process is yet to be known.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Mrinal K
authors.initials: MK
authors.lastname: Das
authors.affiliation: National Institute of Nutrition, Hyderabad, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Basak
authors.affiliation: Institute for Surgical Research, Department of Cardiology, Centre for Heart Failure Research, Oslo University Hospital-Rikshospitalet, University of Oslo, Norway.
authors.forename: M Shakil
authors.initials: MS
authors.lastname: Ahmed
authors.affiliation: Institute for Surgical Research, Department of Cardiology, Centre for Heart Failure Research, Oslo University Hospital-Rikshospitalet, University of Oslo, Norway.
authors.forename: Håvard
authors.initials: H
authors.lastname: Attramadal
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: a.k.duttaroy@medisin.uio.no.
authors.forename: Asim K
authors.initials: AK
authors.lastname: Duttaroy
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics; D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor
keywords: Angiogenesis; CTGF; FABP4; HTR8/SVneo; IL-8; Tube formation