Activation of pregnane X receptor inhibits experimental dermal fibrosis

Annals of the Rheumatic Diseases

Volumn 72, Issue 4, 2013, Pages 621-625

  Beyer, Christian ^a   Skapenko, Alla ^b   Distler, Alfiya ^a   Dees, Clara ^a   Reichert, Helena ^a   Munoz, Louis ^a   Leipe, Jan ^b   Schulze Koops, Hendrik ^b   Distler, Oliver ^c   Schett, Georg ^a   Distler, Jörg H W ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 13; INTERLEUKIN 4; MESSENGER RNA; PREGNANE X RECEPTOR; SMAD2 PROTEIN; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL COUNT; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DOWN REGULATION; GENE; GENE ACTIVATION; IMMUNOHISTOCHEMISTRY; INTERLEUKIN 13 GENE; INTRACELLULAR SIGNALING; MOUSE; MYOFIBROBLAST; NONHUMAN; PATHOGENESIS; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; REMISSION; SKIN FIBROSIS; SKINFOLD; TH2 CELL;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; BLEOMYCIN; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; DERMIS; DISEASE MODELS, ANIMAL; FIBROBLASTS; FIBROSIS; MICE; MICE, INBRED BALB C; MICE, INBRED DBA; PREGNENOLONE CARBONITRILE; RECEPTORS, STEROID; SCLERODERMA, SYSTEMIC; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 84874412823     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2012-202476     Document Type: Article

References (20)

1. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;360:1989-2003.
2. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 2007;117:557-67. (Pubitemid 46348510)
3. Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 2012;18:1028-40.
4. Jinnin M, Ihn H, Yamane K, et al. Interleukin-13 stimulates the transcription of the human alpha2 (I) collagen gene in human dermal fibroblasts. J Biol Chem 2004;279:41783-91. (Pubitemid 39313625)
5. Lee CG, Homer RJ, Zhu Z, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta (1). J Exp Med 2001;194:809-21. (Pubitemid 32983016)
6. Di Masi A, De Marinis E, Ascenzi P, et al. Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects. Mol Aspects Med 2009;30:297-343.
7. Haughton EL, Tucker SJ, Marek CJ, et al. Pregnane X receptor activators inhibit human hepatic stellate cell transdifferentiation in vitro. Gastroenterology 2006;131:194-209. (Pubitemid 44015746)
8. Marek CJ, Tucker SJ, Konstantinou DK, et al. Pregnenolone-16alpha- carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms. Biochem J 2005;387:601-8. (Pubitemid 40685693)
9. Shah YM, Ma X, Morimura K, et al. Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kappaB target gene expression. Am J Physiol Gastrointest Liver Physiol 2007;292:G1114-22. (Pubitemid 46557773)
10. Wang H, Venkatesh M, Li H, et al. Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice. J Clin Invest 2011;121:3220-32.
11. Kliewer SA, Moore JT, Wade L, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998;92:73-82. (Pubitemid 28053299)
12. Akhmetshina A, Palumbo K, Dees C, et al. Activation of canonical Wnt signalling is required for TGF-beta-mediated fibrosis. Nat Commun 2012;3:735.
13. Dees C, Akhmetshina A, Zerr P, et al. Platelet-derived serotonin links vascular disease and tissue fibrosis. J Exp Med 2011;208:961-72.
14. Beyer C, Schramm A, Akhmetshina A, et al. beta-catenin is a central mediator of pro-fibrotic Wnt signaling in systemic sclerosis. Ann Rheum Dis 2012;71:761-7.
15. Beyer C, Reich N, Schindler SC, et al. Stimulation of soluble guanylate cyclase reduces experimental dermal fibrosis. Ann Rheum Dis 2012;71:1019-26.
16. Beyer C, Schett G, Distler O, et al. Animal models of systemic sclerosis: prospects and limitations. Arthritis Rheum 2010;62:2831-44.
17. Avouac J, Furnrohr BG, Tomcik M, et al. Inactivation of the transcription factor STAT-4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis. Arthritis Rheum 2011;63:800-9.
18. Kaviratne M, Hesse M, Leusink M, et al. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. J Immunol 2004;173:4020-9. (Pubitemid 39280766)
19. Hasegawa M, Fujimoto M, Kikuchi K, et al. Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis. J Rheumatol 1997;24:328-32. (Pubitemid 27104098)
20. Dubrac S, Elentner A, Ebner S, et al. Modulation of T lymphocyte function by the pregnane X receptor. J Immunol 2010;184:2949-57.