title: Angiopoietin-like protein 4 (ANGPTL4) is induced by high glucose in retinal pigment epithelial cells and exhibits potent angiogenic activity on retinal endothelial cells.
abstract: OBJECTIVE
  Hyperglycaemia has been identified as major risk factor for diabetic retinopathy (DR). It is widely accepted that the progression of DR is mainly due to a local imbalance of pro- versus anti-angiogenic factors in the retina. In this study, we investigated whether retinal pigment epithelial (RPE) cells produced pro-angiogenic factors under high glucose (HG) conditions in vitro.
  
  
  METHODS
  Cultured human retinal endothelial (RE) cells were exposed to conditioned medium from retinal pigment epithelium cells (ARPE-19) grown in HG medium and assessed for tube formation. Based on the expression profiles of ARPE-19, we investigated whether ANGPTL4 was a major angiogenic factor released from ARPE-19 under HG conditions using cultured human RE cells as the test system for experiments with recombinant protein, conditioned medium from ARPE-19 and RNA interference (RNAi).
  
  
  RESULTS
  The conditioned medium from ARPE-19 cultured under HG conditions promoted tube formation of cultured human RE cells. GeneChip analysis showed that ANGPTL4 was one of the highest upregulated genes under HG conditions. In addition, recombinant ANGPTL4 promoted all of the elements of angiogenesis in human RE cells in vitro. The results of experiments using conditioned medium from ARPE-19 combined with RNAi demonstrated that ANGPTL4 was a major angiogenic factor released from ARPE-19 under HG conditions.
  
  
  CONCLUSIONS
  ANGPTL4 was induced by high glucose in RPE cells and exhibited potent angiogenic activity on RE cells. Our results are unique and may potentially add a new candidate to the long list of molecules involved in diabetic retinopathy.
authors: Department of Metabolic Disorder, Diabetes Research Center, Research Institute, Tokyo, Japan.
authors: Hirotaka
authors: H
authors: Yokouchi
authors: Koki
authors: K
authors: Eto
authors: Wataru
authors: W
authors: Nishimura
authors: Norio
authors: N
authors: Takeda
authors: Yasushi
authors: Y
authors: Kaburagi
authors: Shuichi
authors: S
authors: Yamamoto
authors: Kazuki
authors: K
authors: Yasuda
mesh_terms: D042682:Angiopoietins / Q000096:biosynthesis / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D042682:Angiopoietins; D012333:RNA, Messenger; C118117:angiopoietin 4