Additive Inhibitory Effect of Experimentally Induced Hepatic Cirrhosis by Agonists of Peroxisome Proliferator Activator Receptor gamma and Retinoic Acid Receptor.

Authors: Bruck, R  Weiss, S  Aeed, H  Pines, M  Halpern, Z  Zvibel, I 
Citation: Bruck R, etal., Dig Dis Sci. 2008 Jul 2.
Pubmed: (View Article at PubMed) PMID:18594976
DOI: Full-text: DOI:10.1007/s10620-008-0336-5

Peroxisome proliferator activator receptor (PPAR) ligands prevent liver fibrosis, while the role of all-trans retinoic acid (ATRA) and its metabolite 9-cis retinoic acid (9-cis RA) is less clear. We have investigated the ability of the combination of PPARgamma ligand rosiglitazone (RSG) and of ATRA to prevent liver fibrosis. In vivo treatment with RSG or ATRA reduced fibrotic nodules, spleen weight, and hydroxyproline levels in rat model of thioacetamide-induced liver fibrosis. The combination of ATRA + RSG caused the strongest inhibition, accompanied by decreased expression of collagen I, alpha-smooth muscle actin, TGFbeta1, and TNFalpha. In vitro studies showed that PPARgamma ligand 15-deoxy-Delta12,14-prostaglandinJ(2)[PJ(2)] and RXR ligand 9-cis RA or PJ(2) and ATRA inhibited proliferation of hepatic stellate cells HSC-T6. 9-cis RA inhibited c-jun levels and also inhibited expression of its receptor RXRalpha in HSC-T6 cells. The combination of PPAR-gamma and RAR agonists demonstrated an additive effect in the inhibition of TAA-induced hepatic fibrosis, due to inhibition of HSC proliferation and reduction of profibrotic TGFbeta1 and proinflammatory TNFalpha.


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CRRD Object Information
CRRD ID: 2301874
Created: 2008-11-05
Species: All species
Last Modified: 2008-11-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.