title: Bosentan ameliorates the expression of fibrotic related growth factors and collagen-1 in diabetic mice.
abstract: OBJECTIVE
  To investigate the potential beneficial effect of bosentan in ameliorating fibrotic agents in diabetic mice.
  
  
  METHODS
  Male 6-week old C57BL/6 mice were divided into 3 groups (N=20): Control group, diabetes mellitus (DM) group and DM-B group (diabetes with bosentan group). Streptozotocin (STZ) was injected as 200 mg/Kg for single dose, i.p. (intraperitoneal injection). Fasting blood glucose (FBG) was measured at 0-, 1-, 2-week after STZ injection to confirm that diabetes was induced in the mice. Bosentan (100mg/Kg) and placebo was given i.g. (intragastric administration) once a day immediately after STZ injection for 18 weeks. The mRNA expression of tissue growth factor beta (TGF-b), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and collagen-1 were evaluated by RT-PCR and real-time PCR. Differences in the data between the groups were compared by Student t-test for independent samples.
  
  
  RESULTS
  After 18 weeks of diabetic situation, FBG of DM-B mice was significantly higher than that of control mice and was similar with that of DM mice (DM mice vs. control mice, p<0.001; DM-B vs. control mice, p<0.001; DM mice vs. DM-B mice, p>0.05). The cardiac VEGF mRNA (a potent angiogenic factor) level in DM-B mice was significantly higher than DM mice (p<0.01). The heart of DM-B mice also showed lower expression of fibrotic genes (TGF-b, CTGF and collagen-1) than DM mice (p<0.01).
  
  
  CONCLUSIONS
  These findings indicate the potential usefulness of an ET receptor antagonist bosentan in the amelioration of fibrotic agents, which may promote tissue fibrosis. This may provide a promising therapeutical strategy for diabetic cardiac fibrosis.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing-China. dryangb@yahoo.com.cn
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Zhen-Guo
authors.initials: ZG
authors.lastname: Shi
authors.forename: Quan-Zhou
authors.initials: QZ
authors.lastname: Feng
mesh_terms: D000818:Animals; D000077300:Bosentan; D003094:Collagen / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005355:Fibrosis / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D013311:Streptozocin; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D065128:Endothelin Receptor Antagonists; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D003094:Collagen; D000077300:Bosentan