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PDGF-induced proliferation of smooth muscular cells is related to the regulation of CREB phosphorylation and Nur77 expression

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Summary

This study examined the relationship between PDGF-induced proliferation of vascular smooth muscle cells (VSMCs) and Nur77 expression and the effect of atorvastatin on VSMC proliferation and Nur77 in PDGF-treated VSMCs. Rat VSMCs were isolated and cultured. After incubation with atorvastatin or Nur77 siRNA, the cells were stimulated with PDGF and detected for BrdU incorporation to measure the proliferation of the VSMCs. Quantitative PCR and Western blotting were used to determine the Nur77 protein and the CREB phosphorylation level, to observe their relations with PDGF-induced VSMC proliferation. Our results showed that PDGF increased the BrdU incorporation in VSMCs, suggesting that it induced the proliferation of the cells. The VSMC proliferation was associated with increased Nur77 expression and elevated CREB phosphorylation. Atorvastatin inhibited the PDGF-induced VSMC proliferation, suppressed Nur77 expression. After silencing of Nur77 gene, the PDGF-induced VSMC proliferation was decreased. It was concluded that PDGF-induced VSMC proliferation was related to the Nur77 expression and CREB phosphorylation. Atorvastatin reduced the Nur77 expression and, at the same time, inhibited the VSMC proliferation.

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References

  1. Welt FG, Rongers C. Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc Biol, 2002,22(11): 1769–1776

    Article  PubMed  CAS  Google Scholar 

  2. Topol EJ, Seruys PW. Frontiers in interventional cardiology. Circulation, 1998,98(17):1802–820

    PubMed  CAS  Google Scholar 

  3. Law RE, Meehan WP, Xi XP, et al. Troglitazone inhibits vascular smooth muscles cell growth and intimal hyperplasia. J Clin Invest, 1996,98(8):1897–1905

    Article  PubMed  CAS  Google Scholar 

  4. Law RE, Goetze S, Xi XP, et al. Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation, 2002,101(11):1311–1318

    Google Scholar 

  5. de Vries CJ, van Achterberg TA, Horrevoets AJ, et al. Differential display identification of 40 genes with altered expression in activated human smooth muscle cells. Local expression in atherosclerotic lesions of smags, smooth muscle activation-specific genes. J Biol Chem, 2000, 275(31):23939–23947

    Article  PubMed  Google Scholar 

  6. Baker KD, Shewchuk LM, Kozlova T, et al. The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Cell, 2003,113(6):731–742

    Article  PubMed  CAS  Google Scholar 

  7. Wang Z, Benoit G, Liu J, et al. Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature, 2003,423(6939):555–560

    Article  PubMed  CAS  Google Scholar 

  8. Fahrner TJ, Carroll SL, Milbrandt J. The NGFI-B protein, an inducible member of the thyroid/steroid receptor family, is rapidly modified posttranslationally. Mol Cell Biol, 1990,10(12):6454–6459

    PubMed  CAS  Google Scholar 

  9. Wilson TE, Fahrner TJ, Johnston M, et al. Identification of the DNA binding site for NGFI-B by genetic selection in yeast. Science, 1991,252(5010):1296–1300

    Article  PubMed  CAS  Google Scholar 

  10. Arkenbout EK, van Bragt M, Eldering E, et al. TR3 orphan receptor is expressed in vascular endothelial cells and mediates cell cycle arrest. Arterioscler Thromb Vasc Biol, 2003,23(9):1535–1540

    Article  PubMed  CAS  Google Scholar 

  11. Martinez-González J, Badimon L. The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells. Cardiovasc Res, 2005,65(3): 609–618

    Article  PubMed  Google Scholar 

  12. Pei L, Castrillo A, Tontonoz P. Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77. Mol Endocrinol, 2006, 20(4):786–794

    Article  PubMed  CAS  Google Scholar 

  13. Peter I. Bonta PI, Claudia M, et al. Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses. Arterioscler Thromb Vasc Biol, 2006,26(10): 2288–2294

    Article  Google Scholar 

  14. Weissberg PL, Bennett MR. Atherosclerosis—an inflammatory disease. N Engl J Med, 1999,340(24):115–126

    Google Scholar 

  15. Martinez-Gonzalez L, Lina Badimon L. The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells. Cardiovasc Res, 2005, 65(3):609–618

    Article  PubMed  CAS  Google Scholar 

  16. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell, 1995,83(6):841–850

    Article  PubMed  CAS  Google Scholar 

  17. Claudel T, Leibowitz MD, Fievet C, et al. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. Proc Natl Acad Sci USA, 2001,98(5):2610–2615

    Article  PubMed  CAS  Google Scholar 

  18. Harant H, Lindley IJ. Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Res, 2004,32(17): 5280–5290

    Article  PubMed  CAS  Google Scholar 

  19. de Léséleuc L, Denis F. Inhibition of apoptosis by Nur77 through NF-κB activity modulation. Cell Death and Differ, 2006,13(2):293–300

    Article  Google Scholar 

  20. Arkenbout EK, de Waard V, van Bragt M, et al. 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(12):1530–1535

    Article  PubMed  CAS  Google Scholar 

  21. de Waard V, Arkenbout EK, Vos M, et al. TR3 nuclear orphan receptor prevents cyclic stretch-induced proliferation of venous smooth muscle cells. Am J Pathol, 2006, 168(6):2027–2035

    Article  PubMed  Google Scholar 

  22. Pires NM, Pols TW, de Vries MR, et al. Activation of nuclear receptor Nur77 by 6-mercaptopurine protects against neointima formation. Circulation, 2007,115(4): 493–500

    Article  PubMed  CAS  Google Scholar 

  23. Nomiyama T, Nakamachi T, Gizard F, et al. 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(44): 33467–33476

    Article  PubMed  CAS  Google Scholar 

  24. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxymethylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol, 2001,21(11):1712–1729

    Article  PubMed  CAS  Google Scholar 

  25. Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med, 2002, 8(11):1257–1262

    Article  PubMed  CAS  Google Scholar 

  26. Kohno M, Shinomiya K, Abe S, et al. Mizushige, Inhibition of migration and proliferation of rat vascular smooth muscle cells by a new HMG-CoA reductase inhibitor, pravastatin. Hypertens Res, 2002,25(2):279–285

    Article  PubMed  CAS  Google Scholar 

  27. Porter KE, Naik J, Turner NA, et al. Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration. J Vasc Surg, 2002,36(1):150–157

    Article  PubMed  Google Scholar 

  28. Hernández-Presa MA, Ortego M, Tuñón J, et al. Simvastatin reduces NF-κB activity in peripheral mononuclear and in plaque cells of rabbit atheroma more markedly than lipid lowering diet. Cardiovasc Res, 2003,57(1):168–177

    Article  PubMed  Google Scholar 

  29. Pei L, Castrillo A, Chen M, et al. Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli. J Biol Chem, 2005, 280(32):29265–29272

    Article  Google Scholar 

  30. Bonta PI, van Tiel CM, Vos M, et al. Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses. Arterioscler Thromb Vasc Biol, 2006,26(10): 2288–2294

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Tongren Hospital, Wuhan University, Wuhan, 430060, China

    Liyue Wang  (王丽岳) & Xiaoyan Dong  (董晓雁)

  2. Department of Cardiology, Union Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430022, China

    Wei Zhou  (周 微), Qiutang Zeng  (曾秋棠) & Yi Mao  (毛 奕)

Authors
  1. Liyue Wang  (王丽岳)
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  2. Xiaoyan Dong  (董晓雁)
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  3. Wei Zhou  (周 微)
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  4. Qiutang Zeng  (曾秋棠)
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  5. Yi Mao  (毛 奕)
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Corresponding author

Correspondence to Yi Mao  (毛 奕).

Additional information

This project was supported by a grant from the Program for Scientific Research of Municipal Government (No. 2009-WW76).

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Wang, L., Dong, X., Zhou, W. et al. PDGF-induced proliferation of smooth muscular cells is related to the regulation of CREB phosphorylation and Nur77 expression. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 169–173 (2011). https://doi.org/10.1007/s11596-011-0245-2

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  • DOI: https://doi.org/10.1007/s11596-011-0245-2

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