title: Therapeutic effect of alprostadil in diabetic nephropathy: possible roles of angiopoietin-2 and IL-18.
abstract: OBJECTIVE
  To investigate the role of angiopoietin-2 (Ang-2) and IL-18 in the pathogenesis of diabetic nephropathy (DN) and the molecular mechanisms through which alprostadil protects renal function.
  
  
  METHODS
  DN was induced by streptozotocin and intraperitoneal injection of alprostadil was given to diabetic mice. After 2, 4 and 8 weeks of alprostadil treatment, the mRNA and protein expression of kidney Ang-2 and IL-18 were detected by reverse transcription PCR, Western blot and immunohistochemistry analyses. Mouse glomerular endothelial cells (GEnCs) were cultured in high glucose and treated with alprostadil. After transfection with an Ang-2-pcDNA and Ang-2-siRNA, both Ang-2 and IL-18 expression were measured by Western blot analyses.
  
  
  RESULTS
  Alprostadil treatment caused a significant decrease in the renal damage parameters. Both Ang-2 and IL-18 were significantly increased in DN mice and in GEnCs cultured in high glucose; however, their expression was greatly reduced by alprostadil treatment. Ang-2 could also increase IL-18 expression in cultured endothelial cells under high glucose, and this response was partially blocked by Ang-2 siRNA.
  
  
  CONCLUSIONS
  Ang-2 and IL-18 may be associated with the development and progression of DN in mice. Alprostadil treatment can protect renal function by reducing proteinuria. These effects are mediated, at least in part, through down-regulation of Ang-2 and IL-18 expression.
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, The People's Republic of China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Luo
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Zhenqiong
authors.initials: Z
authors.lastname: Li
authors.forename: Jianshe
authors.initials: J
authors.lastname: Liu
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000527:Alprostadil / Q000627:therapeutic use*; D042702:Angiopoietin-2 / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D005947:Glucose / Q000008:administration & dosage; D006442:Glycated Hemoglobin / Q000378:metabolism; D020382:Interleukin-18 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064804:Urological Agents / Q000627:therapeutic use*
chemical_list: D000527:Alprostadil; D042702:Angiopoietin-2; D001786:Blood Glucose; D017931:DNA Primers; D005947:Glucose; D006442:Glycated Hemoglobin; D020382:Interleukin-18; D064804:Urological Agents