Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effect of Mulberry Extracts on Angiogenesis in Porcine Pulmonary Artery Endothelial Cells

오디 추출물의 혈관신생 억제 효과

  • Lee, Suk-Hee (Division of Biological Sciences, Research Center of Bioactive Materials, Chonbuk National University) ;
  • Kim, Hwan-Gyu (Division of Biological Sciences, Research Center of Bioactive Materials, Chonbuk National University)
  • 이숙희 (전북대학교 자연과학대학 생물과학부, 생리활성물질연구소) ;
  • 김환규 (전북대학교 자연과학대학 생물과학부, 생리활성물질연구소)
  • Published : 2008.05.30
⟨ Previous Next ⟩

Abstract

Endothelial cells release proteinases to degrade the extracellular matrix for their migration and sprouting in vivo. In the present study, we investigated the inhibitory effect of mulberry extracts on the migration and sprouting activity of porcine pulmonary artery endothelial cells (PPAECs). Mulberry extracts significantly inhibited migration and sprouting of PPAECs. Mulberry extracts inhibited expressions and secretions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results suggest that the inhibitory effects of mulberry extracts on migration and sprouting of PPAECs are, in part, associated with the decreased secretion of MMP-2 and MMP-9.

본 연구에서는 PPAECs 세포를 이용하여 오디 추출물에 의한 세포의 이동과 발아에 미치는 효과 및 MMPs와 TIMPs의 분비에 미치는 효과를 조사하여 다음과 같은 결과를 얻었다. PPAECs 세포의 이동에 미치는 오디 추출물의 효과를 조사한 결과, 오디 추출물 농도 80 ${\mu}g/ml$에서 대조군에 비해 이동이 약 36% 억제되었다. 혈관내피세포의 발아 역시, 오디추출물 농도 80 ${\mu}g/ml$에서 PPAECs 세포의 발아가 대조군에 비해 약 50% 억제되었다. PPAECs 세포의 MMPs 및 TIMPs 분비에 미치는 오디 추출물의 효과를 조사한 결과, 오디 추출물 농도 80 ${\mu}g/ml$에서 MMP-2의 분비는 약 45% 감소되었으며, MMP-9의 분비는 약 33% 감소되었다. TIMP-1은 오디 추출물 농도 80 ${\mu}g/ml$에서 분비가 약 51% 억제되었으나, TIMP-2는 오디 추출물 농도 80 ${\mu}g/ml$에서 분비가 약 150% 증가되었다. 이상의 결과를 요약하면, 오디 추출물에 의해 유도된 혈관내피세포의 이동 및 발아 억제는 부분적으로 MMP-2 및 MMP-9의 분비 감소에 의한 것이라 여겨진다.

Keywords

References

  1. Anita, E. Y., A. N. Murphy and W. G. Stetler-Stevenson. 1998. 72 kDa gelatinase (gelatinase A): structure, activation, regulation, and substrate specificity, pp. 85-113, In Parks, W. C. and R. P. Mecham (eds), Matrix metalloproteinases, Academic Press., London.
  2. Bergers, G., R. Brekken, G. McMahon, T. H. Vu, T. Itoh, K. Tamaki, K. Tanzawa, P. Thorpe, S. Itohara, Z. Werbrn and D. Hanahanm. 2000. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2, 737-744. https://doi.org/10.1038/35036374
  3. Bohle, A. S. and H. Kahhoff. 1999. Molecular mechanisms of tumor metasis and angiogenesis. Langenberks Arch. Surg. 384, 133-140. https://doi.org/10.1007/s004230050183
  4. Brown, P. D. 1997. Matrix metalloproteinase inhibitors. Angiogenesis 1, 142-154. https://doi.org/10.1023/A:1018373520193
  5. Chen, C. C., L. K. Liu, J. D. Hsu, H. P. Huang, M. Y. Yang and C. J. Wang. 2005. Mulberry extract inhibit the development of atherosclerosis in cholesterol-fed rabbits. Food Chemistry 91, 601-607. https://doi.org/10.1016/j.foodchem.2004.06.039
  6. Chen, P. N., S. C. Chu, H. L. Chiou, W. H. Kuo, C. L. Chiang and Y. S. Hsieh. 2006. Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett. 235, 248-259. https://doi.org/10.1016/j.canlet.2005.04.033
  7. Chen, Y. and S. H. Tseng. 2007. Pro- and anti-angiogenesis effects of resveratrol. In Vivo 21, 365-370.
  8. Cho A., J. Graves and M. A. Reidy. 2000. Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 20, 2527-2532. https://doi.org/10.1161/01.ATV.20.12.2527
  9. Dor, Y., R. Porat and E. Keshet. 2001. Vascular endothelial growth factor and vascular adjustments to perturbances in oxygen homeostasis. Am. J. Physiol. 280, 1367-1374. https://doi.org/10.1152/ajpcell.2001.280.6.C1367
  10. Ferrara, N. and W. J. Henzel. 1989. Pituitary specific for vascular endothelial cell. Biochem. Biophy. Res. Commu. 161, 852-858.
  11. Havsteen, B. 1983. Flavonoids, a class of natural products of high pharmacological potency. Biochem. Pharmacol. 32, 1141-1145. https://doi.org/10.1016/0006-2952(83)90262-9
  12. Hu, Y., C. Y. Sun, J. Huang, L. Hong, L. Zhang and Z. B. Chu. 2007. Antimyeloma effects of resveratrol through inhibition of angiogenesis. Chin. Med. J. 120, 1672-1677.
  13. Kim, I., S. O. Moon, K. N. Koh, H. Kim, C. S. Uhm, H. J. Kwak, N. G. Kim and G. Y. Koh. 1999. Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting. J. Biol. Chem. 274, 26523-26528. https://doi.org/10.1074/jbc.274.37.26523
  14. Kim, I., H. G. Kim, S. O. Moon, S. W. Chae, J. N. So, K. N. Koh, B. C. Ahn and Koh GY. 2000. Angiopoietin-1 induces endothelial cell sprouting through the activation of focal adhesion kinase and plasmin secretion. Circ. Res. 86, 952-959. https://doi.org/10.1161/01.RES.86.9.952
  15. Kim, M. H., K. C. Ko, S. H. Lim and Y. S. Yu. 1980. Study on the usability of Mulberry fruit (1) Fruit characteristics of Mulberry. Coll. Argic. Bull. SNU. 5, 221-223.
  16. Klagsbrun, M. and P. A. D'Amore. 1991. Regulators of angiogenesis. Annu. Rev. Physiol. 53, 217-239. https://doi.org/10.1146/annurev.ph.53.030191.001245
  17. Kwon, K. B., J. Y. Yang, D. G. Ryu, H. W. Rho, J. S. Kim, J. W. Park, H. R. Kim and B. H. Park. 2001. Vibrio vulnificus cytolysin induces superoxide anion-initiated apoptotic signaling pathway in human ECV304 cells. J. Biol. Chem. 276, 47518-47523. https://doi.org/10.1074/jbc.M108645200
  18. Lamoreaux, W. J., M. E. C. Fitzgerald, A. Reiner, K. A. Hasty and S. T. Chares. 1998. Vascular endothelial growth factor increase release of gelatinase A and decrease of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvas. Res. 55, 29-42. https://doi.org/10.1006/mvre.1997.2056
  19. Millauer, B., S. Wizigmann-Voos, H. Schnurch, R. Martinez, N. P. Moller, W. Risau and A. Ullrich. 1993. High affinity VEGF binding and developmental expression suggest FIk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835-846. https://doi.org/10.1016/0092-8674(93)90573-9
  20. Middleton, E. Jr., C. Kandaswami and T. C. Theoharides. 2000. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev. 52, 673-751.
  21. Moon, S. K., B. Y. Cha and C. H. Kim. 2004. ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: involvement of the ras dependent pathway. J. Cell Physiol. 198, 417-427. https://doi.org/10.1002/jcp.10435
  22. Nagase, H. 1997. Activation mechanisms of matrix metalloproteinases. J. Biol. Chem. 378, 151-160.
  23. Nagase, H. and J. F. Jr. Woessner. 1999. Matrix metalloproteinases. J. Biol. Chem. 274, 21491-21494. https://doi.org/10.1074/jbc.274.31.21491
  24. Neufeld, G., T. Cohen, S. Gengrinovitch and Z. Poltorak. 1999. Vascular endothelical growh factor (VEGF) and its receptor. FASEB J. 13, 9-22. https://doi.org/10.1096/fasebj.13.1.9
  25. Oh, I. S., J. W. Han and H. G. Kim. 2005. Water extracts of Aralia elata root bark enhances migration and matrix metalloproteinases secretion in porcine coronary artery endothelial cells. Biotechnol. Bioprocess Eng. 10, 372-377. https://doi.org/10.1007/BF02931858
  26. Pepper, M. S. 2001. Extracellular proteolysis and angiogenesis. Thromb. Haemost. 86, 346-355. https://doi.org/10.1055/s-0037-1616232
  27. Risau, W. 1997. Mechanisms of angiogenesis. Nature 386, 671-674. https://doi.org/10.1038/386671a0
  28. Seo, D. W., H. Li, C. K. Qu, J. Oh, Y. S. Kim, T. Diaz, B. Wei, J. W. Han and W. G. Stetler-Stevenson. 2006. Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells. J. Biol. Chem. 281, 3711-3721. https://doi.org/10.1074/jbc.M509932200
  29. Sounni, N. E. and A. Noel. 2005. Membrane type-matrix metalloproteinases and tumor progression. Biochemie. 87, 329-342. https://doi.org/10.1016/j.biochi.2004.07.012
  30. Sternlicht, M. D. and Z. Werb. 2001. How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell Devel. Biol. 17, 463-516. https://doi.org/10.1146/annurev.cellbio.17.1.463
  31. Stetler-Stevenson, W. G. and D. W. Seo. 2005. TIMP-2: an endogenous inhibitor of angiogenesis. Trends Mol. Med. 11, 97-103. https://doi.org/10.1016/j.molmed.2005.01.007
  32. Thiennu, H. and Z. Werb. 2000. Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 14, 2123-2133. https://doi.org/10.1101/gad.815400
  33. Woessner, J. F. Jr. 1994. The family of matrix metalloproteinase. Ann. N. Y. Acid. Sci. 732, 11-21. https://doi.org/10.1111/j.1749-6632.1994.tb24720.x

Cited by

  1. Effect of Mulberry (Morus alba L.) Extract on Blood Flow Improvement vol.43, pp.4, 2014, https://doi.org/10.3746/jkfn.2014.43.4.498
  2. Effect of Mulberry Extract Complex on Degenerative Arthritis In Vivo Models vol.45, pp.5, 2016, https://doi.org/10.3746/jkfn.2016.45.5.634
  3. The Effects of Mulberry Extract Consumption on the Serum Levels of Oxidant and Inflammatory Factors in Middle-aged Women with Rheumatoid Factors vol.13, pp.8, 2012, https://doi.org/10.5762/KAIS.2012.13.8.3561
  4. Analysis of Functional Constituents of Mulberries (Morus alba L.) Cultivated in a Greenhouse and Open Field during Maturation vol.44, pp.10, 2015, https://doi.org/10.3746/jkfn.2015.44.10.1588
  5. Animal and Clinical Study of the Efficacy of Mulberry Extract Complex on Degenerative Arthritis vol.30, pp.3, 2015, https://doi.org/10.6116/kjh.2015.30.3.25.
  6. Beneficial Effects of Phyto-Extract Complex (CME) on Degenerative Arthritis vol.28, pp.6, 2013, https://doi.org/10.6116/kjh.2013.28.6.87