PMID- 24342618 OWN - NLM STAT- MEDLINE DCOM- 20140319 LR - 20140127 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 443 IP - 3 DP - 2014 Jan 17 TI - Laminin receptor mediates anti-inflammatory and anti-thrombogenic effects of pigment epithelium-derived factor in myeloma cells. PG - 847-51 LID - S0006-291X(13)02129-3 [pii] LID - 10.1016/j.bbrc.2013.12.060 [doi] AB - Pigment epithelium-derived factor (PEDF) has anti-inflammatory and anti-thrombogenic properties both in cell culture and animal models. Although adipose triglyceride lipase (ATGL) and laminin receptor (LR) are two putative receptors for PEDF, which receptor mainly mediates the beneficial effects of PEDF is largely unknown. In this study, we addressed the issue. siRNA raised against LR (siLR) and siATGL transfection dramatically decreased LR and ATGL levels in human cultured myeloma cells, respectively. Ten nM PEDF significantly reduced vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1) mRNA levels in siCon- or siATGL-transfected myeloma cells, whereas PEDF increased rather than decreased these gene expressions in siLR-transfected cells. Neutralizing antibody directed against LR (LR-Ab) or LR antagonist actually bound to LR and reduced mRNA levels of VEGF, MCP-1, ICAM-1 and PAI-1 in myeloma cells. Further, pre-treatment of LR-Ab or LR antagonist suppressed the binding of PEDF to LR and resultantly blocked the effects of PEDF in myeloma cells. In addition, high concentration of LR agonist mimicked the actions of PEDF on these gene expressions in myeloma cells. This study indicates that PEDF causes anti-angiogenic, anti-inflammatory and anti-thrombogenic reactions in myeloma cells through the interaction with LR. Target domain of LR agonist and antagonist might be involved in the PEDF-signaling to gene suppression in myeloma cells. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Matsui, Takanori AU - Matsui T AD - Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. FAU - Higashimoto, Yuichiro AU - Higashimoto Y AD - Department of Chemistry, Kurume University School of Medicine, Kurume, Japan. FAU - Yamagishi, Sho-ichi AU - Yamagishi S AD - Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. Electronic address: shoichi@med.kurume-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131214 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Anti-Inflammatory Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Eye Proteins) RN - 0 (Fibrinolytic Agents) RN - 0 (Nerve Growth Factors) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Laminin) RN - 0 (Serpins) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (pigment epithelium-derived factor) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 3.1.1.3 (Lipase) RN - EC 3.1.1.3 (PNPLA2 protein, human) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*metabolism MH - Cell Line, Tumor MH - Chemokine CCL2/genetics/metabolism MH - Eye Proteins/*metabolism/pharmacology MH - Fibrinolytic Agents/*metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Lipase/metabolism MH - Mice MH - Multiple Myeloma/*metabolism/pathology MH - Nerve Growth Factors/*metabolism/pharmacology MH - Plasminogen Activator Inhibitor 1/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - RNA, Small Interfering/metabolism MH - Receptors, Laminin/antagonists & inhibitors/*metabolism MH - Serpins/*metabolism/pharmacology MH - Vascular Endothelial Growth Factor A/genetics/metabolism OTO - NOTNLM OT - Inflammation OT - Laminin receptor OT - Myeloma cells OT - PEDF OT - Thrombogenesis EDAT- 2013/12/18 06:00 MHDA- 2014/03/22 06:00 CRDT- 2013/12/18 06:00 PHST- 2013/11/27 00:00 [received] PHST- 2013/12/10 00:00 [accepted] PHST- 2013/12/18 06:00 [entrez] PHST- 2013/12/18 06:00 [pubmed] PHST- 2014/03/22 06:00 [medline] AID - S0006-291X(13)02129-3 [pii] AID - 10.1016/j.bbrc.2013.12.060 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Jan 17;443(3):847-51. doi: 10.1016/j.bbrc.2013.12.060. Epub 2013 Dec 14.