Nur77 suppresses pulmonary artery smooth muscle cell proliferation through Inhibition of the STAT3/Pim-1/NFAT pathway

American Journal of Respiratory Cell and Molecular Biology

Volumn 50, Issue 2, 2014, Pages 379-388

  Liu, Yan ^a,b   Zhang, Jian ^a   Yi, Bing ^b   Chen, Ming ^b   Qi, Jia ^a   Yin, You ^c   Lu, Xiaotong ^a   Jasmin, Jean Francois ^d   Sun, Jianxin ^b  

^a SHANGHAI JIAO TONG UNIVERSITY   (China)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

^c SECOND MILITARY MEDICAL UNIVERSITY   (China)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Orphan nuclear receptor Nur77; Proliferation; Pulmonary artery hypertension; Signal transducer and activator of transcription 3; Smooth muscle cells

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; CYCLIN D1; CYCLINE; EARLY GROWTH RESPONSE FACTOR 1; ENDOTHELIN 1; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MONOCROTALINE; NUCLEAR RECEPTOR NUR77; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR BB; PROTEIN KINASE PIM 1; SEROTONIN; STAT3 PROTEIN; SURVIVIN; TRANSCRIPTION FACTOR NFAT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL HYPOXIA; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; DISEASE COURSE; ENZYME INHIBITION; GENE OVEREXPRESSION; GENE TARGETING; LUNG ALVEOLUS CELL; MALE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PULMONARY ARTERY; PULMONARY HYPERTENSION; RAT; SMOOTH MUSCLE FIBER; UPREGULATION;

ANIMALS; CELL DIFFERENTIATION; CELL PROLIFERATION; HYPERTENSION, PULMONARY; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; NFATC TRANSCRIPTION FACTORS; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 1; PROTO-ONCOGENE PROTEINS C-PIM-1; PULMONARY ARTERY; RATS; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; UP-REGULATION;

EID: 84893241434     PISSN: 10441549     EISSN: 15354989     Source Type: Journal    
DOI: 10.1165/rcmb.2013-0198OC     Document Type: Article

References (47)

1. Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004:13S-24S.
2. Archer S, Rich S. Primary pulmonary hypertension: a vascular biology and translational research "work in progress". Circulation 2000;102:2781-2791.
3. Mandegar M, Fung YC, Huang W, Remillard CV, Rubin LJ, Yuan JX. Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res 2004;68:75-103.
4. Perros F, Montani D, Dorfmüller P, Durand-Gasselin I, Tcherakian C, Le Pavec J, Mazmanian M, Fadel E, Mussot S, Mercier O, et al. Plateletderived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2008;178:81-88.
5. Garat CV, Fankell D, Erickson PF, Reusch JE, Bauer NN, McMurtry IF, Klemm DJ. Platelet-derived growth factor BB induces nuclear export and proteasomal degradation of CREB via phosphatidylinositol 3-kinase/Akt signaling in pulmonary artery smooth muscle cells. Mol Cell Biol 2006;26: 4934-4948.
6. Schultz K, Fanburg BL, Beasley D. Hypoxia and hypoxia-inducible factor-1alpha promote growth factor-induced proliferation of human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 2006; 290:H2528-H2534.
7. Dempsie Y, MacLean MR. Pulmonary hypertension: therapeutic targets within the serotonin system. Br J Pharmacol 2008;155: 455-462.
8. Lee SH, Channick RN. Endothelin antagonism in pulmonary arterial hypertension. Semin Respir Crit Care Med 2005;26: 402-408.
9. Marcos E, Fadel E, Sanchez O, Humbert M, Dartevelle P, Simonneau G, Hamon M, Adnot S, Eddahibi S. Serotonin-induced smooth muscle hyperplasia in various forms of human pulmonary hypertension. Circ Res 2004;94:1263-1270.
10. Liu Y, Wei L, Laskin DL, Fanburg BL. Role of protein transamidation in serotonin-induced proliferation and migration of pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol 2011;44:548-555.
11. Liu Y, Li M, Warburton RR, Hill NS, Fanburg BL. The 5-HT transporter transactivates the PDGFbeta receptor in pulmonary artery smooth muscle cells. FASEB J 2007;21:2725-2734.
12. Ren W, Watts SW, Fanburg BL. Serotonin transporter interacts with the PDGFb receptor in PDGF-BB-induced signaling and mitogenesis in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2011;300:L486-L497.
13. Morecroft I, Pang L, Baranowska M, Nilsen M, Loughlin L, Dempsie Y, Millet C, MacLean MR. In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension. Cardiovasc Res 2010;85:593-603.
14. Cogolludo A, Moreno L, Lodi F, Frazziano G, Cobeño L, Tamargo J, Perez-Vizcaino F. Serotonin inhibits voltage-gated K1 currents in pulmonary artery smooth muscle cells: role of 5-HT2A receptors, caveolin-1, and KV1.5 channel internalization. Circ Res 2006;98: 931-938.
15. MacLean MR, Dempsie Y. Serotonin and pulmonary hypertension - from bench to bedside? Curr Opin Pharmacol 2009;9:281-286.
16. Liu D, Jia H, Holmes DI, Stannard A, Zachary I. Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDRmediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1. Arterioscler Thromb Vasc Biol 2003;23:2002-2007.
17. Mart́inez-Gonzá lez J, Badimon L. The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells. Cardiovasc Res 2005;65:609-618.
18. Nomiyama T, Nakamachi T, Gizard F, Heywood EB, Jones KL, Ohkura N, Kawamori R, Conneely OM, Bruemmer D. The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation. J Biol Chem 2006;281:33467-33476.
19. Zeng H, Qin L, Zhao D, Tan X, Manseau EJ, Van Hoang M, Senger DR, Brown LF, Nagy JA, Dvorak HF. Orphan nuclear receptor TR3/Nur77 regulates VEGF-A-induced angiogenesis through its transcriptional activity. J Exp Med 2006;203:719-729.
20. Zhao Y, Bruemmer D. NR4A orphan nuclear receptors: transcriptional regulators of gene expression in metabolism and vascular biology. Arterioscler Thromb Vasc Biol 2010;30:1535-1541.
21. Hamers AA, Vos M, Rassam F, Marinković G, Kurakula K, van Gorp PJ, de Winther MP, Gijbels MJ, de Waard V, de Vries CJ. Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis. Circ Res 2012;110:428-438.
22. Arkenbout EK, de Waard V, van Bragt M, van Achterberg TA, Grimbergen JM, Pichon B, Pannekoek H, de Vries CJ. Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice. Circulation 2002;106:1530-1535.
23. Pires NM, Pols TW, de Vries MR, van Tiel CM, Bonta PI, Vos M, Arkenbout EK, Pannekoek H, Jukema JW, Quax PH, et al. Activation of nuclear receptor Nur77 by 6-mercaptopurine protects against neointima formation. Circulation 2007;115:493-500.
24. You B, Jiang YY, Chen S, Yan G, Sun J. The orphan nuclear receptor Nur77 suppresses endothelial cell activation through induction of IkappaBalpha expression. Circ Res 2009;104:742-749.
25. Shin HJ, Lee BH, Yeo MG, Oh SH, Park JD, Park KK, Chung JH, Moon CK, Lee MO. Induction of orphan nuclear receptor Nur77 gene expression and its role in cadmium-induced apoptosis in lung. Carcinogenesis 2004;25:1467-1475.
26. Dolinay T, Kaminski N, Felgendreher M, Kim HP, Reynolds P, Watkins SC, Karp D, Uhlig S, Choi AM. Gene expression profiling of target genes in ventilator-induced lung injury. Physiol Genomics 2006;26: 68-75.
27. Li P, Liu Y, Yi B, Wang G, You X, Zhao X, Summer R, Qin Y, Sun J. MicroRNA-638 is highly expressed in human vascular smooth muscle cells and inhibits PDGF-BB-induced cell proliferation and migration through targeting orphan nuclear receptor NOR1. Cardiovasc Res 2013;99:185-193.
28. Darragh J, Soloaga A, Beardmore VA, Wingate AD, Wiggin GR, Peggie M, Arthur JS. MSKs are required for the transcription of the nuclear orphan receptors Nur77, Nurr1 and Nor1 downstream of MAPK signalling. Biochem J 2005;390:749-759.
29. Lam BY, Zhang W, Ng DC, Maruthappu M, Roderick HL, Chawla S. CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors. J Neurochem 2010;112:1065-1073.
30. Paulin R, Courboulin A, Meloche J, Mainguy V, Dumas de la Roque E, Saksouk N, Cô té J, Provencher S, Sussman MA, Bonnet S. Signal transducers and activators of transcription-3/Pim1 axis plays a critical role in the pathogenesis of human pulmonary arterial hypertension. Circulation 2011;123:1205-1215.
31. Paulin R, Meloche J, Jacob MH, Bisserier M, Courboulin A, Bonnet S. Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 2011;301:H1798-H1809.
32. Bonnet S, Rochefort G, Sutendra G, Archer SL, Haromy A, Webster L, Hashimoto K, Bonnet SN, Michelakis ED. The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci USA 2007;104: 11418-11423.
33. Paulin R, Courboulin A, Barrier M, Bonnet S. From oncoproteins/tumor suppressors to microRNAs, the newest therapeutic targets for pulmonary arterial hypertension. J Mol Med (Berl) 2011;89: 1089-1101.
34. Morty RE, Nejman B, Kwapiszewska G, Hecker M, Zakrzewicz A, Kouri FM, Peters DM, Dumitrascu R, Seeger W, Knaus P, et al. Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 2007;27:1072-1078.
35. Bai L, Yu Z, Qian G, Qian P, Jiang J, Wang G, Bai C. SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells. Respir Physiol Neurobiol 2006;152:83-91.
36. Liu X, Chen X, Zachar V, Chang C, Ebbesen P. Transcriptional activation of human TR3/nur77 gene expression by human Tlymphotropic virus type I Tax protein through two AP-1-like elements. J Gen Virol 1999;80:3073-3081.
37. McEvoy AN, Murphy EA, Ponnio T, Conneely OM, Bresnihan B, FitzGerald O, Murphy EP. Activation of nuclear orphan receptor NURR1 transcription by NF-kappa B and cyclic adenosine 59-monophosphate response element-binding protein in rheumatoid arthritis synovial tissue. J Immunol 2002;168: 2979-2987.
38. Kim H, Lee JE, Kim BY, Cho EJ, Kim ST, Youn HD. Menin represses JunD transcriptional activity in protein kinase C theta-mediated Nur77 expression. Exp Mol Med 2005;37:466-475.
39. Ginnan R, Sun LY, Schwarz JJ, Singer HA. MEF2 is regulated by CaMKIId2 and a HDAC4-HDAC5 heterodimer in vascular smooth muscle cells. Biochem J 2012;444:105-114.
40. Mathew R, Huang J, Shah M, Patel K, Gewitz M, Sehgal PB. Disruption of endothelial-cell caveolin-1alpha/raft scaffolding during development of monocrotaline-induced pulmonary hypertension. Circulation 2004;110:1499-1506.
41. Courboulin A, Paulin R, Giguè re NJ, Saksouk N, Perreault T, Meloche J, Paquet ER, Biardel S, Provencher S, Cô té J, et al. Role for miR-204 in human pulmonary arterial hypertension. J Exp Med 2011;208: 535-548.
42. Meloche J, Paulin R, Courboulin A, Lambert C, Barrier M, Bonnet P, Bisserier M, Roy M, Sussman MA, Agharazii M, et al. RAGEdependent activation of the oncoprotein Pim1 plays a critical role in systemic vascular remodeling processes. Arterioscler Thromb Vasc Biol 2011;31:2114-2124.
43. Lin B, Kolluri SK, Lin F, Liu W, Han YH, Cao X, Dawson MI, Reed JC, Zhang XK. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 2004;116:527-540.
44. Mohan HM, Aherne CM, Rogers AC, Baird AW, Winter DC, Murphy EP. Molecular pathways: the role of NR4A orphan nuclear receptors in cancer. Clin Cancer Res 2012;18:3223-3228.
45. Chen YL, Jian MH, Lin CC, Kang JC, Chen SP, Lin PC, Hung PJ, Chen JR, Chang WL, Lin SZ, et al. The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy. Mol Pharmacol 2008;74:1046-1058.
46. Jacobs CM, Boldingh KA, Slagsvold HH, Thoresen GH, Paulsen RE. ERK2 prohibits apoptosis-induced subcellular translocation of orphan nuclear receptor NGFI-B/TR3. J Biol Chem 2004;279:50097-50101.
47. Bristow MR. Beta-adrenergic receptor blockade in chronic heart failure. Circulation 2000;101:558-569.