title: The Suppression of Kallistatin on High-Glucose-Induced Proliferation of Retinal Endothelial Cells in Diabetic Retinopathy.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is a severe ocular complication of diabetes. Kallistatin has multiple biological functions including anti-inflammation and antiangiogenesis. Our aim was to detect the level of kallistatin in the vitreous of proliferative DR (PDR) and its effect on proliferation, migration, and tube formation of human retinal endothelial cells (HRECs) under high glucose in an in vitro model.
  
  
  METHODS
  Vitreous humor samples were obtained through pars plana vitrectomy from 7 nondiabetic patients with idiopathic macular holes or idiopathic preretinal membranes and 10 PDR patients. The vitreous levels of kallistatin were measured by ELISA. HRECs were cultured with different concentrations of glucose and 1,000 nM kallistatin. The proliferation of HRECs was evaluated by a Cell Counting Kit-8 assay. Cell migration was assessed by using Transwell chambers. Cell sprouting was detected by tube formation assay. The RNA interference technique was used to create the knockdown of the kallistatin gene in HRECs for evaluating its effect on the proliferation, migration, and tube formation of HRECs.
  
  
  RESULTS
  The vitreous levels of kallistatin were significantly lower in PDR patients in comparison with nondiabetic control patients (p < 0.05). Compared with 5 mM of normal glucose treatment, high glucose (30 mM) in culture significantly increased the proliferation and migration of HRECs, which was attenuated by 1,000 nM kallistatin. In addition, 1,000 nM kallistatin was shown to suppress high-glucose-induced tube formation and the expression of vascular endothelial growth factor of HRECs. Furthermore, the knockdown of kallistatin enhanced the proliferation, migration, and tube formation of HRECs.
  
  
  CONCLUSIONS
  Our data indicated that kallistatin might be a potent inhibitory factor for PDR. The molecule plays its role by inhibiting high-glucose-induced proliferation of HRECs. The findings suggest that the upregulation of kallistatin might be an effective strategy for PDR prevention.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xing
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhang
authors.forename: Lihua
authors.initials: L
authors.lastname: Kang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Gaoqin
authors.initials: G
authors.lastname: Liu
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhu
authors.forename: Huaijin
authors.initials: H
authors.lastname: Guan
authors.forename: Peirong
authors.initials: P
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000166:cytology / Q000187:drug effects; D015843:Serpins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; C051324:kallistatin; D005947:Glucose