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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李心予 | |
| dc.contributor.author | Chi-Hao Chang | en |
| dc.contributor.author | 張耆豪 | zh_TW |
| dc.date.accessioned | 2021-06-17T00:40:33Z | - |
| dc.date.available | 2013-02-16 | |
| dc.date.copyright | 2012-02-16 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-01-18 | |
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Tholozan, F.M., et al., FGF-2 release from the lens capsule by MMP-2 maintains lens epithelial cell viability. Mol Biol Cell, 2007. 18(11): p. 4222-31. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66525 | - |
| dc.description.abstract | 在腫瘤的生成和轉移過程中，淋巴管新生是一個很重要的機制。目前關於淋巴管新生的機制研究尚未完全了解。神經鞘氨醇 1-磷酸鹽 (Sphingosine 1-phosphate, S1P)屬於小分子水解磷酸酯，透過和其受器的結合，進而調控許多不同的反應，包括細胞增生、細胞分化、發炎反應和血管新生等反應。前人的研究指出神經鞘氨醇 1-磷酸鹽在體內外皆能促進淋巴管新生。在我們的研究也發現在人類臍靜脈內皮細胞 (Human umbilical vein endothelial cells, HUVECs)中，神經鞘氨醇 1-磷酸鹽會促進C型血管內皮生長因子 (Vascular endothelial growth facter-C, VEGF-C)的表現，進而調控淋巴管標記因子的表現。藉由核酸干擾技術，我們證實神經鞘氨醇 1-磷酸鹽調控人類臍靜脈內皮細胞淋巴管新生是透過第二型基質金屬蛋白酶 (Matrix metalloproteinase-2, MMP-2)和第一型纖維母細胞生長因子接受器 (Fibroblast growth receptor-1, FGFR-1)之訊息傳導路徑，另外此機制是透過纖維母細胞生長因子-1 (Fibroblast growth factor-1, FGF-1)依賴傳導路徑，而非纖維母細胞生長因子-2 (FGF-2)。本實驗結果顯示出神經鞘氨醇 1-磷酸鹽對於調控淋巴管新生是一個很重要的因子。 | zh_TW |
| dc.description.abstract | Lymphangiogenesis is an essential process in regulating tumor growth and metastasis. Sphingosine 1-phosphate (S1P) is a potent bioactive phospholipid, which acts as a ligand for a family of G protein-coupled S1P receptors. Through binding to these receptors, S1P modulates multiple biological processes, including cell proliferation and differentiation, inflammatory responses, and angiogenesis. Previous reports showed that S1P induces lymphangiogenesis both in vitro and in vivo. In our present study, we demonstrated that S1P induces vascular endothelial growth factor receptor (VEGF)-C expression and further upregulates lymphatic marker expressions in human umbilical vein endothelial cells (HUVECs). We previously showed that activation of lysophophatidic acid (LPA) receptors enhanced VEGF-C expression through transactivating the epidermal growth factor receptor (EGFR). In contrast, S1P-induced VEGF-C expression was blocked by treatment with SU5402, a fibroblast growth factor (FGF) receptor inhibitor, while an EGFR inhibitor has no effect. By using FGFR-1 and matrix metalloproteinase (MMP)-2 small interfering (si)RNA, we demonstrated that S1P induced HUVECs lymphangiogenesis is mediated through a MMP-2/FGFR-1 -dependent pathway. In addition, S1P-induced phosphorylation of FGFR-1 was blocked by treatment with an MMP inhibitor. Moreover, we also demonstrated that FGF-1, but not FGF-2, participates in the transactivation process.These results demonstrate a novel transactivating signaling processes activated by S1P. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T00:40:33Z (GMT). No. of bitstreams: 1 ntu-101-R98b41015-1.pdf: 1056797 bytes, checksum: b3b940549702b9e0dc8347855b871bcf (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 致謝................................................................................................................i
中文摘要.......................................................................................................ii ABSTRACT……………………………………………………………….iii INTRODUCTION.........................................................................................1 Sphingosine 1-phosphate (S1P)…………………………………..…………......1 Lymphangiogenesis…………..………………………………….…………….1 S1P and Lymphangiogenesis……………………………………….…………..2 Vascular Endothelial Growth Factors (VEGFs) and VEGF receptors…………..…..3 Matrix metalloproteinases (MMPs) and transactivation of tyrosine kinase receptor.....4 Fibroblast Growth Factors (FGFs) and FGF receptors……………………….…..5 THE AIM OF THIS STUDY………………………………………………8 MATERIAL AND METHOD……………………………………………...9 Reagents……………………………………………………………………...9 Cell culture…………………………...……………………………………..10 Determination of FGFR-1 phosphorylation by an enzyme-linked immunosorbent assay (ELISA)……………………………………………………………………..10 Determination of VEGF-C protein expression by an enzyme-linked immunosorbent assay (ELISA)……………………………………………………………….11 Sphingosine 1-phosphate stimulation…………………………….…………….12 siRNA and shRNA eletroporation…………………………………..………….12 RNA isolation and reverse-transcription (RT)………………..………………….13 Quantitative real-time PCR………………………………….…………….….13 Statistical analysis………………………………………………………...…15 RESULTS....................................................................................................16 FGF receptor expression profiles in HUVECs…………………………………..16 S1P-induced VEGF-C expression in HUVECs is mediated through FGFR-1 transactivation………………………………………………………………16 S1P induces FGFR-1 phosphorylation in HUVECs……………………………...17 S1P-induced FGFR-1 phosphorylation is blocked by MMPs inhibitor……………..18 S1P-induced VEGF-C expression in HUVECs is mediated through an MMP-2-dependent mechanism………………………………………………..18 S1P -induced VEGF-C mRNA expression is mediated through FGF-1 but not FGF-2………………………………………………………………………19 S1P upregulates the lymphatic markers, Prox-1 and LYVE-1, through an MMP-2/FGFR-1-dependent pathway…………………………………………..20 S1P-induced VEGF-C is mediated by S1P1……………………………………..20 DISCUSSION…………………………………………………………….22 REFERENCE……………………………………………………………..26 FIGURES…………………………………………………………………34 Figure 1.........................................................................................................34 Figure 2...... ..................................................................................................36 Figure 3.........................................................................................................38 Figure 4.........................................................................................................40 Figure 5.........................................................................................................42 Figure 6.........................................................................................................44 Figure 7.........................................................................................................46 Figure 8.........................................................................................................48 Figure 9.........................................................................................................50 Figure 10........................................................................................................52 | |
| dc.language.iso | zh-TW | |
| dc.subject | 神經鞘氨醇 1-磷酸鹽 | zh_TW |
| dc.subject | 人類臍靜脈內皮細胞 | zh_TW |
| dc.subject | 淋巴管新生 | zh_TW |
| dc.subject | 纖維母細胞受器-1 | zh_TW |
| dc.subject | C型血管內皮細胞生長因子 | zh_TW |
| dc.subject | human umbilical vein endothelial cells (HUVECs) | en |
| dc.subject | sphingosine 1-phosphate (S1P) | en |
| dc.subject | vascular endothelial growth factor C (VEGF-C) | en |
| dc.subject | fibroblast growth factor receptor-1 (FGFR1) | en |
| dc.subject | transactivation | en |
| dc.subject | lymphangiogenesis | en |
| dc.title | 利用人類臍靜脈內皮細胞探討S1P調控VEGF-C及淋巴標記表現機制之研究 | zh_TW |
| dc.title | The signaling mechanism of sphingosine 1-phosphate-regulated vascular endothelial growth factor-C and lymphatic marker expressions in human umbilical cord vein endothelial cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳俊宏,黃偉邦,陳思原 | |
| dc.subject.keyword | 神經鞘氨醇 1-磷酸鹽,C型血管內皮細胞生長因子,纖維母細胞受器-1,淋巴管新生,人類臍靜脈內皮細胞, | zh_TW |
| dc.subject.keyword | sphingosine 1-phosphate (S1P),vascular endothelial growth factor C (VEGF-C),fibroblast growth factor receptor-1 (FGFR1),transactivation,lymphangiogenesis,human umbilical vein endothelial cells (HUVECs), | en |
| dc.relation.page | 53 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-01-19 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究所 | zh_TW |
| 顯示於系所單位： | 動物學研究所 | |
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