Cell-specific PPARγ deficiency establishes anti-inflammatory and anti-fibrogenic properties for this nuclear receptor in non-parenchymal liver cells

Journal of Hepatology

Volumn 59, Issue 5, 2013, Pages 1045-1053

  Morán Salvador, Eva ^a   Titos, Esther ^a,b   Rius, Bibiana ^a   González Périz, Ana ^a,b   García Alonso, Verónica ^a   López Vicario, Cristina ^a   Miquel, Rosa ^a   Barak, Yaacov ^d   Arroyo, Vicente ^a,b   Clària, Joan ^a,b,c  

^a INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c UNIVERSITY OF BARCELONA   (Spain)

^d UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Fibrosis; Hepatic stellate cells; Hepatocytes; Inflammation; Kupffer cells; PPAR

Indexed keywords

ALANINE AMINOTRANSFERASE; ALPHA SMOOTH MUSCLE ACTIN; CARBON TETRACHLORIDE; CASPASE 3; CASPASE 7; CRE RECOMBINASE; CXCL2 CHEMOKINE; CYCLOOXYGENASE 2; HYDROXYPROLINE; INTERLEUKIN 1BETA; INTERLEUKIN 6; LACTATE DEHYDROGENASE; MONOCYTE CHEMOTACTIC PROTEIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FIBROGENESIS; GENE DELETION; HEPATITIS; HETEROZYGOSITY; IMMUNOCYTOCHEMISTRY; INFLAMMATORY INFILTRATE; KUPFFER CELL; LIPID PEROXIDATION; LIVER CELL; LIVER FIBROSIS; LIVER INJURY; LIVER SLICE; LOXP SITE; MACROPHAGE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; STELLATE CELL; UPREGULATION;

4-HNE; 4-HYDROXYNONENAL; ADIPOCYTE FATTY ACID-BINDING PROTEIN 4-CRE (HSC-SPECIFIC PPARΓ DEFICIENT MICE); ALANINE AMINOTRANSFERASE; ALB-CRE; ALBUMIN-CRE (HEPATOCYTE-SPECIFIC PPARΓ DEFICIENT MICE); ALT; AP2-CRE; ASPARTATE AMINOTRANSFERASE; AST; CARBON TETRACHLORIDE; CCL(4); FIBROSIS; HEPATIC STELLATE CELLS; HEPATOCYTES; HSCS; IL; INFLAMMATION; INTERLEUKIN; KUPFFER CELLS; LACTATE DEHYDROGENASE; LDH; LIPOPOLYSACCHARIDE; LPS; LYSM-CRE; LYSOZYME M-CRE (MACROPHAGE-SPECIFIC PPARΓ DEFICIENT MICE); NAFLD; NF-ΚB; NON-ALCOHOLIC FATTY LIVER DISEASE; NUCLEAR FACTOR-KB; PCLS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR Γ; PPARΓ; PRECISION-CUT LIVER SLICES; THIAZOLIDINEDIONES; TNF-Α; TUMOR NECROSIS FACTOR Α; TZD;

ACTINS; ANIMALS; CARBON TETRACHLORIDE; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DRUG-INDUCED LIVER INJURY; HEPATIC STELLATE CELLS; HEPATOCYTES; INFLAMMATION; LIVER CIRRHOSIS; MACROPHAGES; MICE; MICE, KNOCKOUT; PPAR GAMMA; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TISSUE INHIBITOR OF METALLOPROTEINASE-1;

EID: 84885957361     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2013.06.023     Document Type: Article

References (30)

1. S.J. Bensinger, and P. Tontonoz Integration of metabolism and inflammation by lipid-activated nuclear receptors Nature 454 2008 470 477
2. R.A. Daynes, and D.C. Jones Emerging roles of PPARs in inflammation and immunity Nat Rev Immunol 2 2002 748 759
3. F. Marra, E. Efsen, R.G. Romanelli, A. Caligiuri, S. Pastacaldi, and G. Batignani Ligands of PPARgamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells Gastroenterology 119 2000 466 478
4. T. Miyahara, L. Schrum, R. Rippe, S. Xiong, H.F. Yee Jr., and K. Motomura Peroxisome proliferator-activated receptors and hepatic stellate cell activation J Biol Chem 275 2000 35715 35722
5. J. Yu, S. Zhang, E.S. Chu, M.Y. Go, R.H. Lau, and J. Zhao PPARgamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro Int J Biochem Cell Biol 42 2010 948 957
6. M.D. Yang, Y.M. Chiang, R. Higashiyama, K. Asahina, D.A. Mann, and J. Mann Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator-activated receptor γ in hepatic stellate cells for their antifibrotic effect Hepatology 55 2012 1271 1281
7. A. Galli, D.W. Crabb, E. Ceni, R. Salzano, T. Mello, and G. Svegliati-Baroni Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro Gastroenterology 122 2002 1924 1940
8. I.A. Leclercq, C. Sempoux, P. Stärkel, and Y. Horsmans Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats Gut 55 2006 1020 1029
9. L. Li, J. Tao, J. Davaille, C. Feral, A. Mallat, and J. Rieusset 15-deoxy-Delta 12,14-prostaglandin J2 induces apoptosis of human hepatic myofibroblasts. A pathway involving oxidative stress independently of peroxisome-proliferator-activated receptors J Biol Chem 276 2001 38152 38158
10. A. Chawla, Y. Barak, L. Nagy, D. Liao, P. Tontonoz, and R.M. Evans PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation Nat Med 7 2001 48 52
11. E. Morán-Salvador, M. López-Parra, V. García-Alonso, E. Titos, M. Martínez-Clemente, and A. González-Périz Role for PPARγ in obesity-induced hepatic steatosis as determined by hepatocyte- and macrophage-specific conditional knockouts FASEB J 25 2011 2538 2550
12. Y. Barak, M.C. Nelson, E.S. Ong, Y.Z. Jones, P. Ruiz-Lozano, and K.R. Chien PPARgamma is required for placental, cardiac, and adipose tissue development Mol Cell 4 1999 585 595
13. W. He, Y. Barak, A. Hevener, P. Olson, D. Liao, and J. Le Adipose-specific PPARgamma knockout causes insulin resistance in fat and liver but not in muscle Proc Natl Acad Sci U S A 100 2003 15712 15717
14. C. Postic, M. Shiota, K.D. Niswender, T.L. Jetton, Y. Chen, and J.M. Moates Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase J Biol Chem 274 1999 305 315
15. B.E. Clausen, C. Burkhardt, W. Reith, R. Renkawitz, and I. Forster Conditional gene targeting in macrophages and granulocytes using LysMcre mice Transgenic Res 8 1999 265 277
16. E. Titos, B. Rius, A. González-Périz, C. López-Vicario, E. Morán-Salvador, and M. Martínez-Clemente Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype J Immunol 187 2011 5408 5418
17. R. Bataller, and D.A. Brenner Liver fibrosis J Clin Invest 115 2005 209 218
18. A.L. Hevener, J.M. Olefsky, D. Reichart, M.T. Nguyen, G. Bandyopadyhay, and H.Y. Leung Macrophage PPARgamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones J Clin Invest 117 2007 1658 1669
19. L. Wu, C. Yan, M. Czader, O. Foreman, J.S. Blum, and R. Kapur Inhibition of PPARγ in myeloid-lineage cells induces systemic inflammation, immunosuppression, and tumorigenesis Blood 119 2012 115 126
20. K. Kinoshita, Y. Iimuro, J. Fujimoto, Y. Inagaki, K. Namikawa, and H. Kiyama Targeted and regulable expression of transgenes in hepatic stellate cells and myofibroblasts in culture and in vivo using an adenoviral Cre/loxP system to antagonise hepatic fibrosis Gut 56 2007 396 404
21. T. Kisseleva, M. Cong, Y. Paik, D. Scholten, C. Jiang, and C. Benner Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis Proc Natl Acad Sci U S A 109 2012 9448 9453
22. K.E. Govoni, J.E. Wergedal, L. Florin, P. Angel, D.J. Baylink, and S. Mohan Conditional deletion of insulin-like growth factor-I in collagen type-1 alpha2-expressing cells results in postnatal lethality and a dramatic reduction in bone accretion Endocrinology 148 2007 5706 5715
23. S.W. Beaven, K. Wroblewski, J. Wang, C. Hong, S. Bensinger, and H. Tsukamoto Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease Gastroenterology 140 2011 1052 1062
24. J.I. Odegaard, R.R. Ricardo-Gonzalez, A. Red Eagle, D. Vats, C.R. Morel, and M.H. Goforth Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance Cell Metab 7 2008 496 507
25. S.E. Schadinger, N.L. Bucher, B.M. Schreiber, and S.R. Farmer PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes Am J Physiol Endocrinol Metab 288 2005 E1195 E1205
26. B. Sun, and M. Karin NF-kappaB signaling, liver disease and hepatoprotective agents Oncogene 20 2008 6228 6244
27. G. Pascual, A.L. Fong, S. Ogawa, A. Gamliel, A.C. Li, and V. Perissi A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma Nature 437 2005 759 763
28. J.I. Odegaard, R.R. Ricardo-Gonzalez, M.H. Goforth, C.R. Morel, V. Subramanian, and L. Mukundan Macrophage-specific PPARγ controls alternative activation and improves insulin resistance Nature 447 2007 1116 1120
29. K. Fuenzalida, R. Quintanilla, P. Ramos, D. Piderit, R.A. Fuentealba, and G. Martinez Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis J Biol Chem 282 2007 37006 37015
30. G. Ding, M. Fu, Q. Qin, W. Lewis, H.W. Kim, and T. Fukai Cardiac peroxisome proliferator-activated receptor gamma is essential in protecting cardiomyocytes from oxidative damage Cardiovasc Res 76 2007 269 279