title: Advanced glycation end products of bovine serum albumin-induced endothelial-to-mesenchymal transition in cultured human and monkey endothelial cells via protein kinase B signaling cascades.
abstract: OBJECTIVE
  Advanced glycation end products of BSA (AGE-BSA) participate in the pathogenesis of diabetic vascular disease. However, the role of AGE-BSA in diabetic retinopathy, especially in retinal neovascularization, remains incomplete. This study aimed to determine the contributions of AGE-BSA in the endothelial-to-mesenchymal transition (EnMT) of cultured human and monkey endothelial cell lines and the mechanism that may be related with the transition.
  
  
  METHODS
  Monkey choroid-retinal endothelial cells (RF/6A) and human umbilical vein endothelial cells (HUVEC) were cultured in Dulbecco's modified Eagle's Medium (DMEM) and Ham's F12 medium containing 200 mg/l AGE-BSA. The expression of VE-cadherin, β-catenin, vimentin, N-cadherin, and protein kinase B (AKT2) was observed by immunocytochemistry and flow cytometry. Cell motility was determined by migration assays; the endothelial function of the formatting tube was measured by tube formation assays, while the change in the polarity was measured using resistance instruments.
  
  
  RESULTS
  The characteristics of EnMT included loss of endothelial markers of VE-cadherin and β-catenin, which were replaced by mesenchymal markers of vimentin and N-cadherin, enhanced migration and tube formation, and diminished polarity. AGE-BSA contributed to upregulation of the protein expression of VE-cadherin and β-catenin and downregulation of protein expression of vimentin and N-cadherin, leading to enhanced migration and tube formation and diminished polarity. During this process, expression of AKT2 was upregulated.
  
  
  CONCLUSIONS
  AGE-BSA can induce EnMT of cultured human and monkey endothelial cells. The signal pathway involving AKT2 may play a role in this process.
authors.affiliation: Weifang Medical University, Weifang, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Ma
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D000882:Haplorhini; D006801:Humans; D007150:Immunohistochemistry; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D051057:Proto-Oncogene Proteins c-akt