title: Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis.
abstract: OBJECTIVE
  To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferator-activated receptor-gamma (PPAR-gamma), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.
  
  
  METHODS
  Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation. Animals were killed at 1, 2, or 4 wk after surgery.
  
  
  RESULTS
  The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type I gene expression and liver hydroxy-proline levels. Accumulation of alpha-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of gamma-glutamyl-transferase (GGT).
  
  
  CONCLUSIONS
  Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.
authors.affiliation: Dipartimento di Medicina Interna, University of Florence, Viale Morgagni 85, Florence I-50134, Italy. f.marra@dmi.unifi.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
authors.forename: Raffaella
authors.initials: R
authors.lastname: DeFranco
authors.forename: Gaia
authors.initials: G
authors.lastname: Robino
authors.forename: Erica
authors.initials: E
authors.lastname: Novo
authors.forename: Eva
authors.initials: E
authors.lastname: Efsen
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pastacaldi
authors.forename: Elena
authors.initials: E
authors.lastname: Zamara
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Lottini
authors.forename: Carlo
authors.initials: C
authors.lastname: Spirli
authors.forename: Mario
authors.initials: M
authors.lastname: Strazzabosco
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002779:Cholestasis / Q000188:drug therapy* / Q000473:pathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione