title: Hypoxia potentiates transforming growth factor-beta expression of hepatocyte during the cirrhotic condition in rat liver.
abstract: OBJECTIVE
  Many studies have reported that hypoxia might be associated with angiogenesis and fibrogenesis, and the level of transforming growth factor-beta1 (TGF-beta1) was increased in fibrotic liver and maximal at cirrhosis. Therefore, we examined the expression of TGF-beta1, phosphorylated-Smad2/3 (p-Smad2/3) of the TGF-beta immediate down stream signaling system and hypoxic status during hepatic fibrogenesis.
  
  
  METHODS
  Fibrosis of rats was induced by carbon tetrachloride. Collagens were detected with Azan stain. Immunohistochemistry and immunoblotting was used.
  
  
  RESULTS
  TGF-beta1 was mainly produced by hypoxic hepatocytes at cirrhosis although myofibroblasts (MFBs) and macrophages producing TGF-beta1 were decreased. Moreover, distribution of p-Smad2/3 in hepatocytes was consistent with those of hypoxic hepatocytes regardless of MFBs. Furthermore, in recovery, most MFBs disappeared, whereas positive reactions of p-Smad2/3 still existed in the hepatocytes of hypoxic areas. Therefore, TGF-beta1 expression in hepatocytes might have been associated with hypoxia.
  
  
  CONCLUSIONS
  We put forward the hypothesis that TGF-beta1 is mainly produced by MFBs and macrophages at early and middle stages of fibrotic processes, but it is predominantly released by hypoxic hepatocytes in the last fibrotic stage or cirrhosis.
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea.
authors.forename: Won-Ii
authors.initials: WI
authors.lastname: Jeong
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Do
authors.forename: Hae-Sun
authors.initials: HS
authors.lastname: Yun
authors.forename: Byoung-Joon
authors.initials: BJ
authors.lastname: Song
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Wie-Jong
authors.initials: WJ
authors.lastname: Kwak
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Ho-Yong
authors.initials: HY
authors.lastname: Park
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology*; D000860:Hypoxia; D015151:Immunoblotting; D007150:Immunohistochemistry; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011336:Probability; D012333:RNA, Messenger / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D015534:Trans-Activators; D003094:Collagen; D002251:Carbon Tetrachloride