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

General

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.
RGD ID:	2301874
Pubmed:	PMID:18594976 (View Abstract at PubMed)
DOI:	DOI:10.1007/s10620-008-0336-5 (Journal Full-text)
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.

RGD Manual Disease Annotations Click to see Annotation Detail View

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Experimental Liver Cirrhosis		ISO	Pparg (Rattus norvegicus)	2301874; 2301874		RGD
Experimental Liver Cirrhosis		IMP		2301874		RGD

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
negative regulation of cell population proliferation		IMP		2301874		RGD

Objects Annotated

Genes (Rattus norvegicus)

Pparg (peroxisome proliferator-activated receptor gamma)

Genes (Mus musculus)

Pparg (peroxisome proliferator activated receptor gamma)

Genes (Homo sapiens)

PPARG (peroxisome proliferator activated receptor gamma)

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