Advertisement

Effect of nuclear factor-kappa B on vascular endothelial growth factor mRNA expression of human pulmonary artery smooth muscle cells in hypoxia

  • Zhang Huanping
  • Xu Yongjian
  • Zhang Zhenxiang
  • Xu Shuyun
  • Ni Wang
  • Chen Shixin
Article

Summary

In order to investigate the effect of nuclear factor-kappa B (NF-κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCsin vitro were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. The NF-κB p65 nuclei positive expression was detected by immunocytochemical technique. The IκBα protein expression was measured by Western blot. RT-PCR was used to detect the VEGF mRNA expression of HPASMCs. The results showed that no significant change was observed in the NF-κB p65 nuclei positive expression of HPASMCs during 6 h−24 h in normoxia, but the levels of NF-κB p65 nuclei positive expression of cultured HPASMCs were significantly increased in hypoxia groups as compared with those in all normoxia groups (P<0.05). The IκBα protein expression of cultured HPASMCs showed no significant change during 6 h−24 h in normoxia, but significantly decreased in hypoxia as comapred with that in normoxia groups (P<0.05). PDTC (1 to 100 μmol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration-dependent manner in hypoxia. In conclusion, NF-κB can be partly translocation activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The inhibition of NF-κB activation can decrease the VEGF mRNA expression. It is suggested that the activation of NF-κB is involved in the VEGF mRNA expression of HPASMCs under hypoxia.

Key words

hypoxia pulmonary artery smooth muscle vascular endothelial growth factor nuclear factor-kappa B 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lenardo M J, Baltimore D. NF-KB: a pleiotropic mediator of inducible and tissue-specific gene control. Cell, 1989, 58: 227PubMedCrossRefGoogle Scholar
  2. 2.
    Barnes P J, Karin M. Nuclear factor-kappa B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med, 1997, 336: 1066PubMedCrossRefGoogle Scholar
  3. 3.
    Ferrara N, Davis-Smith T. The biology of vascular endothelial growth factor. Endocr Rev. 1997. 18: 4PubMedCrossRefGoogle Scholar
  4. 4.
    Sasaki H, Zhu L, Fukuda Set al. Inhibition of NF kappa B activation by pyrrolidine dithiocarbamate prevents in vivo hypoxia/reoxygenation-mediated myocardial angiogenesis. Int J Tissue React. 2000. 22: 93PubMedGoogle Scholar
  5. 5.
    Sasaki H, Ray P S, Zhu Let al. Oxidative stress due to hypoxia/reoxygenation induces angiogenic factor VEGF in adult rat myocardium: possible role of NFkappaB. Toxicology. 2000. 155: 27PubMedCrossRefGoogle Scholar
  6. 6.
    Bausero P, Ben-Mahdi M, Mazucatelli Jet al. Vascular endothelial growth factor is modulated in vascular muscle cells by estradiol, tamoxifen, and hypoxia. Am J Physiol Heart Circ Physiol. 2000: 279(5): H2033PubMedGoogle Scholar
  7. 7.
    Baldwin A S Jr. The NF-κB and IκB protein: new discoveries and insights. Annu Rev Immunol. 1996. 14: 649CrossRefGoogle Scholar
  8. 8.
    Xu Q, Shan Y, Schmedtje J Fet al. Spl increases expression of cyclooxygenase-2 in hypoxia vascular endothelium. Implications for the mechanisms of aortic aneurysm and heart failure. J Biol Chem. 2000. 275: 24 583Google Scholar
  9. 9.
    Matsushita H, Morishita R, Nata Tet al. Hpoxia-induced endothelial apoptosis through nuclear factor-κB (NF-κB)-mediated bcl-2 suppression: in vivo evidence of the importance of NF-κB in endothelial cell regulation. Circ Res. 2000. 86: 974PubMedGoogle Scholar
  10. 10.
    Trubiani O, Di Giulio C, Tripodi Det al. Thymic sensitivity to hypoxia condition in young and old rats. Agedependent expression of NF-kappaB. Exp Gerontol. 2002. 37: 1077PubMedCrossRefGoogle Scholar
  11. 11.
    Xu Y, Stenmark K R, Das Met al. Pulmonary artery smooth muscle cells from chronically hypoxia neonatal calves retain fetal-like and acquire new growth properties. Am J Physiol. 1997. 273: L234PubMedGoogle Scholar
  12. 12.
    Ferrara N, Winer J, Burton T. Aortic smooth muscle cells express and secrete vascular endothelial growth factor. Growth Factors. 1991. 5: 141PubMedCrossRefGoogle Scholar
  13. 13.
    Brogi E, Schatteman G, Wu Tet al. Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Invest. 1996. 97: 469CrossRefGoogle Scholar
  14. 14.
    Selzman C H, Shames B D, McIntyre R C Jret al. The NF-kappa B inhibitory peptide, I kappa B alpha, prevents human smooth muscle proliferation. Ann Thorac Surg. 1999. 67: 1227PubMedCrossRefGoogle Scholar
  15. 15.
    Hoshi S, Goto M, Koyama Net al. Regulation of vascular smooth muscle cell proliferation by nuclear factor-kappa B and its inhibitor I-kappa B. J Biol Chem. 2000. 275: 883PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2004

Authors and Affiliations

  • Zhang Huanping
    • 1
  • Xu Yongjian
    • 1
  • Zhang Zhenxiang
    • 1
  • Xu Shuyun
    • 1
  • Ni Wang
    • 1
  • Chen Shixin
    • 1
  1. 1.Department of Respiratory Medicine, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan

Personalised recommendations