Cross-talk between farnesoid-x-receptor (FXR) and peroxisome proliferator-activated receptor γ contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis

Journal of Pharmacology and Experimental Therapeutics

Volumn 315, Issue 1, 2005, Pages 58-68

  Fiorucci, Stefano ^a,c   Rizzo, Giovanni ^a   Antonelli, Elisabetta ^a   Renga, Barbara ^a   Mencarelli, Andrea ^a   Riccardi, Luisa ^a   Morelli, Antonio ^a   Pruzanski, Mark ^b   Pellicciari, Roberto ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

^b INTERCEPT PHARMACEUTICALS   (United States)

^c POLICLINICO MONTELUCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

6 ETHYLCHENODEOXYCHOLIC ACID; ALPHA SMOOTH MUSCLE ACTIN; CARBON TETRACHLORIDE; CHENODEOXYCHOLIC ACID DERIVATIVE; COLLAGEN TYPE 1; FARNESOID X RECEPTOR; FIBRONECTIN; HYDROXYPROLINE; MESSENGER RNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; ROSIGLITAZONE; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE DUCT LIGATION; CELL ACTIVATION; CELL DIFFERENTIATION; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DOWN REGULATION; DRUG POTENTIATION; GENE EXPRESSION; GENE EXPRESSION REGULATION; LIVER CELL; LIVER CIRRHOSIS; LIVER FIBROSIS; MALE; MORPHOMETRICS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RAT; RODENT; STELLATE CELL; UPREGULATION;

ANIMALS; CELLS, CULTURED; CHENODEOXYCHOLIC ACID; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION; HUMANS; LIVER; LIVER CIRRHOSIS, EXPERIMENTAL; PPAR GAMMA; RATS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RNA, MESSENGER; THIAZOLIDINEDIONES; TRANSCRIPTION FACTORS;

EID: 25644443217     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.105.085597     Document Type: Article

References (31)

1. Bedoucha M, Atzpodien E, and Boelsterli UA (2001) Diabetic KKAy mice exhibit increased hepatic PPARgamma1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones. J Hepatol 35:17-23.
2. Berger J and Moller DE (2002) The mechanisms of action of PPARs. Annu Rev Med 53:409-435.
3. Fiorucci S, Antonelli E, Distrutti E, Severino B, Fiorentina R, Baldoni M, Caliendo G, Santagada V, Morelli A, and Cirino G (2004a) PAR1 antagonism protects against experimental liver fibrosis. Role of proteinase receptors in stellate cell activation. Hepatology 39:365-375.
4. Fiorucci S, Antonelli E, Rizzo G, Renga B, Mencarelli A, Riccardi L, Orlandi S, Pellicciari R, and Morelli A (2004b) The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis. Gastroenterology 14:1444-1456.
5. Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, et al. (1995) Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81:687-693.
6. Friedman SL (2003) Liver fibrosis-from bench to bedside. J Hepatol 38 (Suppl 1):S38-S53.
7. Galli A, Crabb D, Price D, Ceni E, Salzano R, Surrenti C, and Casini A (2000) Peroxisome proliferator-activated receptor gamma transcriptional regulation is involved in platelet-derived growth factor-induced proliferation of human hepatic stellate cells. Hepatology 31:101-108.
8. Galli A, Crabb DW, Ceni E, Salzano R, Mello T, Svegliati-Baroni G, Ridolfi F, Trozzi L, Surrenti C, and Casini A (2002) Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology 122:1924-1940.
9. Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, Galardi C, Wilson JG, Lewis MC, Roth ME, et al. (2000) A regulatory cascade of the nuclear receptors FXR, SHP-1 and LRH-1 represses bile acid biosynthesis. Mol Cell 6:517-526.
10. Hazra S, Xiong S, Wang J, Rippe RA, Krishna V, Chatterjee K, and Tsukamoto H (2004) Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells. J Biol Chem 279:11392-11401.
11. Hellemans K, Michalik L, Dittie A, Knorr A, Rombouts K, De Jong J, Heirman C, Quartier E, Schuit F, Wahli W, et al. (2003) Peroxisome proliferator-activated receptor-beta signaling contributes to enhanced proliferation of hepatic stellate cells. Gastroenterology 124:184-201.
12. Ip E, Farrell G, Hall P, Robertson G, and Leclercq I (2004) Administration of the potent PPARalpha agonist, Wy-14,643, reverses nutritional fibrosis and steatohepatitis in mice. Hepatology 39:1286-1296.
13. Jarvinen HY (2004) Thiazolidinediones. N Engl J Med 351:1106-1117.
14. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, and Lehmann JM (1995) A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor and promotes adipocyte differentiation. Cell 83:813-819.
15. Kon K, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Kitamura T, Takei Y, and Sato N (2002) Pioglitazone prevents early-phase hepatic fibrogenesis caused by carbon tetrachloride. Biochem Biophys Res Commun 291:55-61.
16. Leesnitzer LM, Parks DJ, Bledsoe RK, Cobb JE, Collins JL, Consler TG, Davis RG, Hull-Ryde EA, Lenhard JM, Patel L, et al. (2002) Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662. Biochemistry 41:6640-6650.
17. Lopez-De Leon A and Rojkind M (1985) A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections. J Histochem Cytochem 33:737-743.
18. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, and Shan B (1999) Identification of a nuclear receptor for bile acids. Science (Wash DC) 284:1362-1365.
19. Maloney PR, Parks DJ, Haffner CD, Fivush AM, Chandra G, Plunket KD, Creech KL, Moore LB, Wilson JG, Lewis MC, et al. (2000) Identification of a chemical tool for the orphan nuclear receptor FXR. J Med Chem 43:2971-2974.
20. Marra F, Efsen E, Romanelli RG, Caligiuri A, Pastacaldi S, Batignani G, Bonacchi A, Caporale R, Laffi G, Pinzani M, et al. (2000) Ligands of peroxisome proliferatoractivated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Gastroenterology 119:466-478.
21. Matsusue K, Haluzik M, Lambert G, Yim SH, Gavrilova O, Ward JM, Brewer B Jr, Reitman ML, and Gonzalez FJ (2003) Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Investig 111:737-747.
22. Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, and Rastinejad F (2003) Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol Cell 11:1093-1100.
23. Miyahara T, Schrum L, Rippe R, Xiong S, Yee HF Jr, Motomura K, Anania FA, Willson TM, and Tsukamoto H (2000) Peroxisome proliferator-activated receptors and hepatic stellate cell activation. J Biol Chem 275:35715-35722.
24. Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, et al. (2003) American Heart Association; American Diabetes Association. Thiazolidinedione use, fluid retention and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 108:2941-2948.
25. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, and Bacon BR (2003) Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPARgamma ligand rosiglitazone. Hepatology 38:1008-1017.
26. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, et al. (1999) Bile acids: natural ligands for an orphan nuclear receptor. Science (Wash DC) 284:1365-1368.
27. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, Morelli A, Parks DJ, and Willson TM (2002) 6-α-Ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem 45:3569-3572.
28. Pineda Torra I, Claudel T, Duval C, Kosykh V, Fruchart JC, and Staels B (2003) Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor. Mol Endocrinol 17:259-272.
29. Shi Y, Hon M, and Evans RM (2002) The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. Proc Natl Acad Sci USA 99:2613-2618.
30. Tsukamoto H (2002) Hepatic stellate cells as a target for TZD: can we treat liver fibrosis and type II diabetes at the same time? Hepatology 36:1011-1013.
31. Wang H, Chen J, Hollister K, Sowers LC, and Forman BM (1999) Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 3:543-553.