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Cysteine-rich angiogenic protein 61-induced ectopic mineralization is mediated by activation of matrix metalloproteinases in vascular smooth muscle cells : 혈관 평활근 세포의 CYR61 단백에 의해 매개되는 이소성 무기화 작용은 기질금속단백분해효소의 활성화에 의해 매개된다
DC Field | Value | Language |
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dc.contributor.advisor | 김효수 | - |
dc.contributor.author | 김치훈 | - |
dc.date.accessioned | 2017-07-19T11:08:39Z | - |
dc.date.available | 2017-07-19T11:08:39Z | - |
dc.date.issued | 2016-02 | - |
dc.identifier.other | 000000132757 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133391 | - |
dc.description | 학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과 분자의학 및 바이오제약학 전공, 2016. 2. 김효수. | - |
dc.description.abstract | Background: Cysteine-rich angiogenic protein 61 (CYR61) was reported to be induced by angiotensin II in vascular smooth muscle cells (VSMCs), and it is a key regulatory molecule in ectopic mineralization of osteogenic transdifferentiated VSMCs. But, exact molecular mechanism of CYR61-induced mineralization is unclear, so we explored downstream effector molecule of CYR61.
Methods and Results: VSMCs harvested from thoracic aortas of male C57BL6 mice were transfected with adenoviral vector containing Cyr61 (Ad-CYR61), and then microarray analysis was performed to evaluate the effects of CYR61 on VSMC mineralization. Several matrix metalloproteinases such as MMP-13, MMP-3 and MMP-10 were immediately increased by 7.9, 6.5, and 2.0-folds after 24 hours of transfection. However, tissue inhibitors of metalloproteinases such as TIMP-3 and TIMP-2 were reduced by 52% and 71%, respectively (all p<0.05). Real-time PCR confirmed MMP-13 gene induction by 33±13 folds compared to control adenovirus-transfected VSMCs (p<0.05). Although mRNA expression of MMP-9 was not found to be increased, gelatin zymography showed an augmented enzymatic activity of MMP-9 by Ad-CYR61 transfection, which was significantly decreased by siRNA for MMP-13. In the light microscopic analysis with Von Kossa staining or electron microscopic examinations, dominant negative adenoviral vector for c-Jun and broad spectrum MMP inhibitor doxycycline can minimize or attenuate CYR61-medated ECM disruption or ectopic mineralization. Conclusion: These findings demonstrate that CYR61-mediated MMP activation is important to induce vascular calcification in the milieu of systemic inflammation. Therapies targeting to CYR61 or MMPs may modulate vascular calcification and could have clinical implications. | - |
dc.description.tableofcontents | Introdunction 1
Materials and Methods 4 Results 15 Discussion 22 Conclusion 27 Reference 28 Tables and Figures 34 Abstract in Korean 43 | - |
dc.format | application/pdf | - |
dc.format.extent | 950191 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 융합과학기술대학원 | - |
dc.subject | Cysteine-rich angiogenic protein 61 | - |
dc.subject | Matrix metalloproteinase | - |
dc.subject | Mineralization | - |
dc.subject | Vascular calcification | - |
dc.subject.ddc | 610 | - |
dc.title | Cysteine-rich angiogenic protein 61-induced ectopic mineralization is mediated by activation of matrix metalloproteinases in vascular smooth muscle cells | - |
dc.title.alternative | 혈관 평활근 세포의 CYR61 단백에 의해 매개되는 이소성 무기화 작용은 기질금속단백분해효소의 활성화에 의해 매개된다 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Chi-Hoon Kim | - |
dc.description.degree | Master | - |
dc.citation.pages | 44 | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2016-02 | - |
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