title: Differential expression of transforming growth factor-beta and its receptors in hepatocytes and nonparenchymal cells of rat liver after CCl4 administration.
abstract: OBJECTIVE
  Transforming growth factor-beta (TGF-beta) is a family of multifunctional proteins that regulate hepatocyte proliferation, and biosynthesis of the extracellular matrix. In this study we examined whether modulation of TGF-beta receptor expression contributes to the liver diseases.
  
  
  METHODS
  The mRNA expression of TGF-beta1, TGF-beta type I receptor (TGFbetaRI), TGF-beta type II receptor (TGFbetaRII) and TGF-beta type III receptor (TGFbetaRIII) in rat livers injured by CCl4 administration was studied by Northern blotting. The mRNA expression patterns were confirmed by in situ hybridization.
  
  
  RESULTS
  The peak of TGF-beta1 mRNA expression was observed 48 h after acute intoxication with CCl4 in nonparenchymal cells. However, the levels of TGFbetaRI and TGFbetaRII mRNA expression decreased from 24 h to 48 h and from 12 h to 48 h, respectively, and returned to the normal level by 72 h. TGFbetaRII mRNA expression was depressed more and for longer than that of TGFbetaRI mRNA. Analysis in separated hepatocytes and nonparenchymal cells from the injured livers indicated that the mRNA changes occurred in hepatocytes. Nonparenchymal cells expressed TGFbetaRI and TGFbetaRII mRNAs at constant levels during liver regeneration. TGFbetaRIII mRNA, which also decreased after 12 h, was not apparent in hepatocytes but only in nonparenchymal cells.
  
  
  CONCLUSIONS
  These observations suggest that: (i) whenever TGF-beta1 is increased in CCl4-treated livers, it may induce liver fibrogenesis via nonparenchymal cells; (ii) the mitoinhibitory effect of TGF-beta1 on hepatocytes is transiently relieved by down-regulation of TGF-beta receptors for 72 h post-damage; and (iii) the resistance to TGF-beta growth inhibition between 24 to 48 h may be predominantly due to down-regulation of the expression of TGFbetaRII.
authors.affiliation: Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Date
authors.forename: K
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: K
authors.initials: K
authors.lastname: Sakitani
authors.forename: K
authors.initials: K
authors.lastname: Shibano
authors.forename: A
authors.initials: A
authors.lastname: Okajima
authors.forename: C
authors.initials: C
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Ogata
authors.forename: T
authors.initials: T
authors.lastname: Okumura
authors.forename: T
authors.initials: T
authors.lastname: Seki
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Kan
authors.forename: W L
authors.initials: WL
authors.lastname: McKeehan
authors.forename: K
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D017403:In Situ Hybridization; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta