후코이단이 혈관 내피세포의 신생혈관 생성 효과 및 관련 유전자의 발현에 미치는 영향
Effect of Fucoidan on Angiogenesis and Gene Expression in Human Umbilical Vein Endothelial Cells
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신생혈관생성은 여러 신생혈관 생성 인자들이 포함되는 중요한 과정이며, 특히 이 과정에서는 섬유아세포증식인자(FGF-2) 는 세포의 증식률과 미세관 형성을 촉진하기 때문에 중요한 신생혈관 생성인자로 여겨진다. 최근 연구에 따르면 해조류에서추출되는 후코이단 다당류 물질이 섬유아세포 증식인자2에 의한 혈관내피세포의 미세관형성을 더욱 촉진한다고 보고하였다. 그러나 섬유아세포 증식인자와 후코이단 복합처리에 따른신생혈관생성 활성에 대한 분자적 메카니즘은 아직 연구가 부족하다. 따라서 본 연구에서는 신생혈관생성 활성을 알아보기위하여 섬유아세포 증식인자와 후코이단 물질의 복합처리에 따른 세포의 증식과 미세관형성률 그리고 세포의 이동율을 측정하였다. 또한 이들의 신생혈관 생성 활성에 관련된 인자를 탐색하기 위하여 VEGF-A, ICAM-1, MMP9, 그리고 ICAM-1 유전자를 연전사 중합연쇄반응으로 평가하였다. 본 연구의 결과에서는 후코이단과 섬유아세포 증식인자 복합처리는 혈관내피세포의 성장률, 미세관 형성률 그리고 세포의 이동률을 촉진하고, 이 과정에서 신생혈관생성 기능과 관련된 STAT3, VEGF-A, MMP9 그리고 ICAM-1의 유전자 발현을 촉진함으로 신생혈관생성활성이 나타나는 것으로 보여진다. 그러나 이러한 유전자발현이 fucoidan/FGF2에 의한 angiogenic 활성 촉진에 직접적인 영향을 미치는 지에 대한 추가적인 연구가 이루어져야 할것으로 생각된다.
Abstract
Angiogenesis is a process including members of the angiogenic factors. In particular, fibroblast growth factor 2 (FGF2) is considered the most potent angiogenic factor because it promotes cell proliferation and tube formation. A recent study reported that fucoidan derived from marine plant potentiated FGF-2 induced tube formation in human endothelial cells. On the other hand, the molecular mechanisms involved in the angiogenic activity of fucoidan and FGF2 are unknown. In this study, a fucoidan treatment promoted angiogenesis induced by FGF2. The effects of fucoidan on FGF2-induced angiogenesis were confirmed by a proliferation assay using a CellTiter96 Aqueous One solution after a treatment with fucoidan and FGF2. The tube formation and wound healing assay for the angiogenic activity were also confirmed. Reverse transcription PCR showed a change in the mRNA of vascular endothelial growth factor-A (VEGF-A), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase9 (MMP9), and the signal transducer and activator of transcription3 (STAT3). In summary, the Fucoidan/FGF2 treatment induced an increase in cell proliferation, improved the tube formation and wound healing activity, and altered the STAT3, VEGF-A, ICAM-1, and MMP9 mRNA expression levels. Further research will be needed to provide a scientific explanation in terms of cell-signaling and confirm the present findings.
참고문헌 (24)
- Carmeliet P, "Angiogenesis in cancer and other diseases", Nature, 407(14), pp.249~257 (2000)
- Folkman J, "Relation of vascular proliferation to tumor growth", Int Rev Exp Pathol, 16, pp.207~248 (1976)
- Yun YR, "Fibroblast growth factors: biology, function, and application for tissue regeneration", J Tissue Eng, pp.218142~ (2010)
- Matou S, "Effect of an oversulfated exopolysaccharide on angiogenesis induced by fibroblast growth factor-2 or vascular endothelial growth factor in vitro", Biochem Pharmacol, 69(5), pp.751~759 (2005)
- Liu F, "Fucoidan extract derived from Undaria pinnatifida inhibits angiogensis by human umbilical vein endothelial cells", Phytomedicine, 19(8-9), pp.797~803 (2012)
- Koyanagi S, "Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities", Biochem Pharmacol, 65(2), pp.173~179 (2003)
- Soeda S, "Oversulfated fucoidan inhibits the basic fibroblast growth factor-induced tube formation by human umbilical vein endothelial cells: it’s possible mechanism of action", Biochim Biophys Acta, 1497(1), pp.127~134 (2000)
- Manzo-Silberman S, "Therapeutic potential of fucoidan in myocardial ischemia", J Cardiovasc Pharmacol, 58(6), pp.626~632 (2011)
- Matou S, "Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro", Thromb Res, 106(4-5), pp.213~221 (2002)
- Beck L Jr, "Vascular development: cellular and molecular regulation", FASEB J, 11(5), pp.365~373 (1997)
- Risau W, "Vasculogenesis", Annu Rev Cell Dev Biol, 11, pp.73~91 (1995)
- Chabut D, "Low molecular weight fucoidan promotes FGF-2-induced vascular tube formation by human endothelial cells, with decreased PAI-1 release and ICAM-1 downregulation", Thromb Res, 113(1), pp.93~95 (2004)
- Zemani F, "Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells", Biochem Pharmacol, 70(8), pp.1167~1175 (2005)
- Ju M, "Simultaneous but not prior inhibition of VEGF165 enhances the efficacy of photodynamic therapy in multiple models of ocular neovascularization", Invest Ophthalmol Vis Sci, 49, pp.662~670 (2008)
- Lai CM, "Inhibition of corneal neovascularization by recombinant adenovirus mediated antisense VEGF RNA", Exp Eye Res, 75(6), pp.625~634 (2002)
- Ferrara N, "The biology of vascular endothelial growth factor", Endocr Rev, 18, pp.4~25 (1997)
- Brown LF, "Vascular permeability factor", vascular endothelial growth factor: a multifunctional angiogenic cytokine, 1997, pp.79, 233~269
- Carmona G, "Activation of Epac stimulates integrin-dependent homing of progenitor cells", Blood, 111(5), pp.2640~2646 (2008)
- Radisavljevic Z, "Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase", AKT, J Biol Chem, pp.2000, 275(27)[DOI]
- Presta M, "Inflammatory cells and chemokines sustain FGF2-induced angiogenesis", Eur Cytokine Netw, 20(2), pp.39~50 (2009)
- Muroski ME, "Matrix metalloproteinase-9", gelatinase B is a putative therapeutic target of chronic obstructive pulmonary disease and multiple sclerosis, 2008, pp.9(1), 34~46
- Chen Z, "STAT3: a critical transcription activator in angiogenesis", Med Res Rev, 28(2), pp.185~200 (2008)
- 제갈승주, "자궁경부상피내종양과 침윤성 편평상피암종의 혈관신생에서 비만세포와 혈관내피성장인자의 발현", 대한임상검사과학회지, 37(3), pp.197~206 (2005), 대한임상검사과학회
- Xie T, "Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis 2", Oncogene, 23(20), pp.3550~3560 (2004)