請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7999
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李士傑(Shyh-Jye Lee) | |
dc.contributor.author | Ying-Hsien Liao | en |
dc.contributor.author | 廖穎嫻 | zh_TW |
dc.date.accessioned | 2021-05-19T18:02:07Z | - |
dc.date.available | 2025-06-24 | |
dc.date.available | 2021-05-19T18:02:07Z | - |
dc.date.copyright | 2015-07-20 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-06-25 | |
dc.identifier.citation | Ambros, V. (2004). 'The functions of animal microRNAs.' Nature 431(7006): 350-355.
Avraham, T., S. Daluvoy, J. Zampell, A. Yan, Y. S. Haviv, S. G. Rockson and B. J. Mehrara (2010). 'Blockade of transforming growth factor-beta1 accelerates lymphatic regeneration during wound repair.' Am J Pathol 177(6): 3202-3214. Bos, F. L., M. Caunt, J. Peterson-Maduro, L. Planas-Paz, J. Kowalski, T. Karpanen, A. van Impel, R. Tong, J. A. Ernst, J. Korving, J. H. van Es, E. Lammert, H. J. Duckers and S. Schulte-Merker (2011). 'CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo.' Circ Res 109(5): 486-491. Clavin, N. W., T. Avraham, J. Fernandez, S. V. Daluvoy, M. A. Soares, A. Chaudhry and B. J. Mehrara (2008). 'TGF-beta1 is a negative regulator of lymphatic regeneration during wound repair.' Am J Physiol Heart Circ Physiol 295(5): H2113-2127. Filipowicz, W., S. N. Bhattacharyya and N. Sonenberg (2008). 'Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?' Nat Rev Genet 9(2): 102-114. Flores, M. V., C. J. Hall, K. E. Crosier and P. S. Crosier (2010). 'Visualization of embryonic lymphangiogenesis advances the use of the zebrafish model for research in cancer and lymphatic pathologies.' Dev Dyn 239(7): 2128-2135. Franzosa, J. A., S. M. Bugel, T. L. Tal, J. K. La Du, S. C. Tilton, K. M. Waters and R. L. Tanguay (2013). 'Retinoic acid-dependent regulation of miR-19 expression elicits vertebrate axis defects.' FASEB J 27(12): 4866-4876. Gore, A. V., K. Monzo, Y. R. Cha, W. Pan and B. M. Weinstein (2012). 'Vascular development in the zebrafish.' Cold Spring Harb Perspect Med 2(5): a006684. Guo, Y., S. Li, J. Qu, S. Wang, Y. Dang, J. Fan, S. Yu and J. Zhang (2011). 'MiR-34a inhibits lymphatic metastasis potential of mouse hepatoma cells.' Mol Cell Biochem 354(1-2): 275-282. Hagerling, R., C. Pollmann, M. Andreas, C. Schmidt, H. Nurmi, R. H. Adams, K. Alitalo, V. Andresen, S. Schulte-Merker and F. Kiefer (2013). 'A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy.' EMBO J 32(5): 629-644. Hogan, B. M., F. L. Bos, J. Bussmann, M. Witte, N. C. Chi, H. J. Duckers and S. Schulte-Merker (2009). 'Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting.' Nat Genet 41(4): 396-398. Isogai, S., N. D. Lawson, S. Torrealday, M. Horiguchi and B. M. Weinstein (2003). 'Angiogenic network formation in the developing vertebrate trunk.' Development 130(21): 5281-5290. Jeltsch, M., T. Tammela, K. Alitalo and J. Wilting (2003). 'Genesis and pathogenesis of lymphatic vessels.' Cell Tissue Res 314(1): 69-84. Jones-Rhoades, M. W. and D. P. Bartel (2004). 'Computational identification of plant microRNAs and their targets, including a stress-induced miRNA.' Mol Cell 14(6): 787-799. Kim, V. N., J. Han and M. C. Siomi (2009). 'Biogenesis of small RNAs in animals.' Nat Rev Mol Cell Biol 10(2): 126-139. Lee, S. J., T. H. Chan, T. C. Chen, B. K. Liao, P. P. Hwang and H. Lee (2008). 'LPA1 is essential for lymphatic vessel development in zebrafish.' FASEB J 22(10): 3706-3715. Kuchler, A. M., E. Gjini, J. Peterson-Maduro, B. Cancilla, H. Wolburg and S. Schulte-Merker (2006). 'Development of the zebrafish lymphatic system requires VEGFC signaling.' Curr Biol 16(12): 1244-1248. Mulligan, T. S. and B. M. Weinstein (2014). 'Emerging from the PAC: studying zebrafish lymphatic development.' Microvasc Res 96: 23-30. Nicoli, S., C. P. Knyphausen, L. J. Zhu, A. Lakshmanan and N. D. Lawson (2012). 'miR-221 is required for endothelial tip cell behaviors during vascular development.' Dev Cell 22(2): 418-429. Nicoli, S., C. Standley, P. Walker, A. Hurlstone, K. E. Fogarty and N. D. Lawson (2010). 'MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis.' Nature 464(7292): 1196-1200. Oka, M., C. Iwata, H. I. Suzuki, K. Kiyono, Y. Morishita, T. Watabe, A. Komuro, M. R. Kano and K. Miyazono (2008). 'Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis.' Blood 111(9): 4571-4579. Okuda, K. S., J. W. Astin, J. P. Misa, M. V. Flores, K. E. Crosier and P. S. Crosier (2012). 'lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish.' Development 139(13): 2381-2391. Oliver, G. (2004). 'Lymphatic vasculature development.' Nat Rev Immunol 4(1): 35-45. Pedrioli, D. M., T. Karpanen, V. Dabouras, G. Jurisic, G. van de Hoek, J. W. Shin, D. Marino, R. E. Kalin, S. Leidel, P. Cinelli, S. Schulte-Merker, A. W. Brandli and M. Detmar (2010). 'miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo.' Mol Cell Biol 30(14): 3620-3634. Shin, K. and S. H. Lee (2014). 'Interplay between Inflammatory Responses and Lymphatic Vessels.' Immune Netw 14(4): 182-186. Srinivasan, R. S. and G. Oliver (2011). 'Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves.' Genes Dev 25(20): 2187-2197. Stacker, S. A., S. P. Williams, T. Karnezis, R. Shayan, S. B. Fox and M. G. Achen (2014). 'Lymphangiogenesis and lymphatic vessel remodelling in cancer.' Nat Rev Cancer 14(3): 159-172. Tammela, T., G. Zarkada, E. Wallgard, A. Murtomaki, S. Suchting, M. Wirzenius, M. Waltari, M. Hellstrom, T. Schomber, R. Peltonen, C. Freitas, A. Duarte, H. Isoniemi, P. Laakkonen, G. Christofori, S. Yla-Herttuala, M. Shibuya, B. Pytowski, A. Eichmann, C. Betsholtz and K. Alitalo (2008). 'Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation.' Nature 454(7204): 656-660. Thisse, C., Thisse, B., Schilling, T.F., Postlethwait, J.H., 1993. Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos. Development 119, 1203-1215. von Bubnoff, A. and K. W. Cho (2001). 'Intracellular BMP signaling regulation in vertebrates: pathway or network?' Dev Biol 239(1): 1-14. Wienholds, E., W. P. Kloosterman, E. Miska, E. Alvarez-Saavedra, E. Berezikov, E. de Bruijn, H. R. Horvitz, S. Kauppinen and R. H. Plasterk (2005). 'MicroRNA expression in zebrafish embryonic development.' Science 309(5732): 310-311. Wigle, J. T. and G. Oliver (1999). 'Prox1 function is required for the development of the murine lymphatic system.' Cell 98(6): 769-778. Yang, Y., J. M. Garcia-Verdugo, M. Soriano-Navarro, R. S. Srinivasan, J. P. Scallan, M. K. Singh, J. A. Epstein and G. Oliver (2012). 'Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos.' Blood 120(11): 2340-2348. Yaniv, K., S. Isogai, D. Castranova, L. Dye, J. Hitomi and B. M. Weinstein (2006). 'Live imaging of lymphatic development in the zebrafish.' Nat Med 12(6): 711-716. Ye, H., X. Liu, M. Lv, Y. Wu, S. Kuang, J. Gong, P. Yuan, Z. Zhong, Q. Li, H. Jia, J. Sun, Z. Chen and A. Y. Guo (2012). 'MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia.' Nucleic Acids Res 40(12): 5201-5214. Zhao, Y. and D. Srivastava (2007). 'A developmental view of microRNA function.' Trends Biochem Sci 32(4): 189-197. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7999 | - |
dc.description.abstract | 血管及淋巴管是循環系統的基本構造,但其在脊椎動物之研究常因皮膚及其他阻隔而增加其困難度。斑馬魚由於其胚胎透明、並有幾種血管螢光魚品系易於研究,近年來已成為血管新生(angiogenesis) 及淋巴管新生(lymphangiogenesis) 的主流模式動物之一。微核醣核酸(miRNAs)在血管新生及淋巴管新生中扮演重要角色,前人研究發現幾種miRNAs在斑馬魚血管內皮細胞高量表現,並發現其中之一miR-221在血管新生成有其功能,但其他miRNAs所扮演角色則仍未知。在本論文中,我重複前人試驗發現在利用流式細胞儀分選出的內皮細胞中,一些miRNAs的表現量於產卵後22-48小時有顯著的變化。其中miR-19c被發現在22-48小時有顯著的上升情形,由已知的研究中知道這個時間點與血管和淋巴管發育皆有所相關,所以我大膽假設miR-19c可能參與血管發育或淋巴管發育。為了釐清這個問題,我以血管螢光轉基因斑馬魚為材料,利用morpholino/miRNA抑制劑與miRNA模擬物(mimic)分別抑制或增加miR-19c的表現來探討miR-19c在斑馬魚發育過程中所扮演的角色。我發現增加miR-19c的表現會造成淋巴血管系統缺陷,但不管是抑制或增加miR-19c的表現皆不明顯影響血管系統。利用微核醣核酸目標預測資料庫(Target Scan)與定量即時聚合酶鏈鎖反應(real-time PCR),我發現transforming growth factor beta 1a (tgfβ1a)為miR-19c的目標基因之一,且增加miR-19c表現可降低tgfβ1a表現量,但tgfβ1a在淋巴管新生成之功能則尚待釐清。總體而言,本研究結果顯示,miR-19c可能經由tgfβ1a來影響斑馬魚淋巴管的發育。 | zh_TW |
dc.description.abstract | Vessel formation, including angiogenesis and lymphangiogenesis, paves the structural foundation of circulation. The study of vessel formation in vertebrates often hinders by the invisibility, but the availability of transparent zebrafish embryos greatly accelerates our understanding in the field. With the addition of several vessel reporter lines, zebrafish has become one of the popular models to explore the regulatory mechanisms of angiogenesis and lymphangiogenesis. microRNAs (miRNAs) have been reported to be involved in regulating angiogenesis and lymphangiogenesis. In particularly, several miRNAs have been shown to be enriched in blood endothelial cells. However, except miR-221, the functional roles of other miRNAs remain unknown. Here, I first validated the enrichment of those miRNAs in endothelial cells from embryos at 22-48 h post fertilization. Interestingly, I found one of miRNAs, miR-19c, increases notably during 22-48 hpf. This time is associated with blood vessel and lymphatic vessel formation, I hypothesized that miR-19c may regulate blood or lymphatic vessel formation.
I performed loss and gain of function analyses by applying antisense morpholino/miRNA inhibitor and miRNA mimic against miR-19c to different transgenic zebrafish lines expressing GFP. I observed that overexpression of miR-19c impaired lymphatic development, but no significant change in blood vascular system was observed in embryos. Transforming growth factor beta1a (tgfβ1a) is a potential target of miR-19c and known lymphangiogenesis regulator. I found significant reduction of the expression of tgfβ1a in embryos injected with miR-19c mimic. The functional link between miR-19c and tgfβ1a still needs to be investigated. Collectively, I conclude that miR-19c is indispensable to lymphatic development in zebrafish possibly via tgfβ1a. | en |
dc.description.provenance | Made available in DSpace on 2021-05-19T18:02:07Z (GMT). No. of bitstreams: 1 ntu-104-R02b21005-1.pdf: 3667420 bytes, checksum: 950f7e79356a4cb7e61923d106257d1e (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 口試委員會審定書 III
誌謝 IV 中文摘要 V Abstract VI Content VIII List of Figures X Introduction 1 miRNAs in vascular development 1 Vascular formation in zebrafish 2 Molecular mechanisms of lymphangiogenesis 4 Materials and Methods 7 Zebrafish maintenance and embryos collection 7 Transgenic zebrafish lines 7 Microinjection 7 Fluorescence-activated cell sorting (FACS) 8 RNA isolation, cDNA preparation, RT-PCR and qPCR for miRNA analyses 8 miR-19c manipulation 9 RNA isolation, cDNA preparation and qPCR for gene expression analyses 10 Whole-mount in situ hybridization 11 Microscopic imaging 12 Statistical analysis 12 Results 13 Expression analysis of blood endothelial cell-enriched microRNAs 13 Expression patterns of zebrafish miR-19c 13 Overexpressing miR-19c affects lymphatic but not blood vessel development 14 Overexpression of miR-19c enhances expression of genes associated with lymphatic vessel development 17 miR-19c reduces tgfβ1a but not lpar1 expression 18 Discussion 20 References 24 Table 30 Figures 31 | |
dc.language.iso | en | |
dc.title | 微核醣核酸(miR-19c)在斑馬魚血管發育扮演角色之探討 | zh_TW |
dc.title | The role of miR-19c in zebrafish vessel development | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 朱家瑩(Chia-Ying Chu),黃聲蘋(Sheng-Ping Hwang),鄭邑荃(Yi-Chuan Cheng),劉薏雯(Yi-Wen Liu) | |
dc.subject.keyword | 斑馬魚,血管新生發育,淋巴管新生發育,微核醣核酸,miR-19c, | zh_TW |
dc.subject.keyword | Angiogenesis,Lymphangiogenesis,Zebrafish,miRNAs,miR-19c, | en |
dc.relation.page | 43 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2015-06-25 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生命科學系 | zh_TW |
dc.date.embargo-lift | 2025-06-24 | - |
顯示於系所單位: | 生命科學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-104-1.pdf 此日期後於網路公開 2025-06-24 | 3.58 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。