Marra F, DeFranco R, Robino G, Novo E, Efsen E, Pastacaldi S, Zamara E, Vercelli A, Lottini B, Spirli C, Strazzabosco M, Pinzani M, Parola M. Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis. World J Gastroenterol 2005; 11(32): 4931-4938 [PMID: 16124041 DOI: 10.3748/wjg.v11.i32.4931]
Corresponding Author of This Article
Professor Fabio Marra, Dipartimento di Medicina Interna, University of Florence, Viale Morgagni 85, Florence I-50134, Italy. f.marra@dmi.unifi.it
Article-Type of This Article
Basic Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Aug 28, 2005; 11(32): 4931-4938 Published online Aug 28, 2005. doi: 10.3748/wjg.v11.i32.4931
Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis
Fabio Marra, Raffaella DeFranco, Gaia Robino, Erica Novo, Eva Efsen, Sabrina Pastacaldi, Elena Zamara, Alessandro Vercelli, Benedetta Lottini, Carlo Spirli, Mario Strazzabosco, Massimo Pinzani, Maurizio Parola
Fabio Marra, Raffaella DeFranco, Eva Efsen, Sabrina Pastacaldi, Benedetta Lottini, Massimo Pinzani, Dipartimento di Medicina Interna and Center for Research, Transfer, and High Education ‘DENOTHE’, University of Florence, Italy
Gaia Robino, Erica Novo, Elena Zamara, Maurizio Parola, Dipartimento di Medicina e Oncologia Sperimentale, University of Turin, Italy
Alessandro Vercelli, Dipartimento di Anatomia, Farmacologia e Medicina Legale, University of Turin, Italy
Carlo Spirli, Mario Strazzabosco, Istituto Veneto di Medicina Molecolare, Padua, Italy
Author contributions: All authors contributed equally to the work.
Supported by the Italian MIUR Grant, No. MM_06315722, by the University of Florence and by the Italian Liver Foundation. Eva Efsen was Supported in Part by the Tode Travel Grant, the Direktør Madsen’s Grant and Fhv. Direktør Nielsen’s Grant (Denmark)
Correspondence to: Professor Fabio Marra, Dipartimento di Medicina Interna, University of Florence, Viale Morgagni 85, Florence I-50134, Italy. f.marra@dmi.unifi.it
Telephone: +39-55-4296475 Fax: +39-55-417123
Received: October 16, 2004 Revised: December 20, 2004 Accepted: December 23, 2004 Published online: August 28, 2005
Abstract
AIM: To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferator-activated receptor-γ (PPAR-γ), 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 α-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 γ-glutamyl-transferase (GGT).
CONCLUSION: 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.
