title: Lysophosphatidic acid alters the expression profiles of angiogenic factors, cytokines, and chemokines in mouse liver sinusoidal endothelial cells.
abstract: OBJECTIVE
  Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we investigated the effects of LPA on the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs.
  
  
  METHODS
  Mouse Lsecs were isolated using CD31-coated magnetic beads. The mRNA expression levels of LPAR's and other target genes were determined by quantitative RT-PCR. The protein levels of angiogenesis factors, cytokines, and chemokines were determined using protein arrays and enzyme immunoassay (EIA). Critical LPAR related signal transduction was verified by using an appropriate chemical inhibitor.
  
  
  RESULTS
  LPAR1 and LPAR3 mRNA's were expressed in mouse LPA-treated Lsecs. Treating Lsecs with a physiological level of LPA significantly enhanced the protein levels of angiogenesis related proteins (cyr61 and TIMP-1), cytokines (C5/C5a, M-CSF, and SDF-1), and chemokines (MCP-5, gp130, CCL28, and CXCL16). The LPAR1 and LPAR3 antagonist ki16425 significantly inhibited the LPA-enhanced expression of cyr61, TIMP-1, SDF-1, MCP-5, gp130, CCL28, and CXCL16, but not that of C5/C5a or M-CSF. LPA-induced C5/C5a and M-CSF expression may have been through an indirect regulation mechanism.
  
  
  CONCLUSIONS
  LPA regulated the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs that was mediated via LPAR1 and LPAR3 signaling. Most of the factors that were enhanced by LPA have been found to play critical roles during liver regeneration. Thus, these results may prove useful for manipulating LPA effects on liver regeneration.
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shou-Lun
authors.initials: SL
authors.lastname: Lai
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Cheng-Maw
authors.initials: CM
authors.lastname: Ho
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Hsi
authors.initials: WH
authors.lastname: Lin
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Fu-Chuo
authors.initials: FC
authors.lastname: Peng
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Hsin
authors.initials: SH
authors.lastname: Kuo
authors.affiliation: Department of Radiation-Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Szu-Yuan
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hong-Shiee
authors.initials: HS
authors.lastname: Lai
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000166:cytology*; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D020543:Proteome / Q000187:drug effects; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: C491850:CCN1 protein, mouse; D017077:Culture Media, Conditioned; D055515:Cysteine-Rich Protein 61; D016207:Cytokines; D008246:Lysophospholipids; D020543:Proteome; D049368:Receptors, Lysophosphatidic Acid; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; C032881:lysophosphatidic acid
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