Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 動物學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65712
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor李士傑
dc.contributor.authorTun-Hao Chanen
dc.contributor.author詹敦皓zh_TW
dc.date.accessioned2021-06-17T00:00:47Z-
dc.date.available2013-07-27
dc.date.copyright2012-07-27
dc.date.issued2012
dc.date.submitted2012-07-16
dc.identifier.citationAlders, M., Hogan, B.M., Gjini, E., Salehi, F., Al-Gazali, L., Hennekam, E.A., Holmberg, E.E., Mannens, M.M., Mulder, M.F., Offerhaus, G.J., Prescott, T.E., Schroor, E.J., Verheij, J.B., Witte, M., Zwijnenburg, P.J., Vikkula, M., Schulte-Merker, S., Hennekam, R.C., 2009. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet 41, 1272-1274.
Alitalo, K., Tammela, T., Petrova, T.V., 2005. Lymphangiogenesis in development and human disease. Nature 438, 946-953.
Bussmann, J., Bos, F.L., Urasaki, A., Kawakami, K., Duckers, H.J., Schulte-Merker, S., 2010. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk. Development 137, 2653-2657.
Chien, M.H., Ku, C.C., Johansson, G., Chen, M.W., Hsiao, M., Su, J.L., Inoue, H., Hua, K.T., Wei, L.H., Kuo, M.L., 2009. Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway. Carcinogenesis 30, 2005-2013.
Contos, J.J., Fukushima, N., Weiner, J.A., Kaushal, D., Chun, J., 2000. Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc Natl Acad Sci U S A 97, 13384-13389.
Contos, J.J., Ishii, I., Fukushima, N., Kingsbury, M.A., Ye, X., Kawamura, S., Brown, J.H., Chun, J., 2002. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol Cell Biol 22, 6921-6929.
Del Giacco, L., Pistocchi, A., Ghilardi, A., 2010. prox1b Activity is essential in zebrafish lymphangiogenesis. PLoS One 5, e13170.
Di, J.M., Zhou, J., Zhou, X.L., Gao, X., Shao, C.Q., Pang, J., Sun, Q.P., Zhang, Y., Ruan, X.X., 2009. Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-C and lymph node metastases in human prostate cancer. Arch Med Res 40, 268-275.
Eichholtz, T., Jalink, K., Fahrenfort, I., Moolenaar, W.H., 1993. The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J 291 ( Pt 3), 677-680.
English, D., Kovala, A.T., Welch, Z., Harvey, K.A., Siddiqui, R.A., Brindley, D.N., Garcia, J.G., 1999. Induction of endothelial cell chemotaxis by sphingosine 1-phosphate and stabilization of endothelial monolayer barrier function by lysophosphatidic acid, potential mediators of hematopoietic angiogenesis. J Hematother Stem Cell Res 8, 627-634.
Francois, M., Caprini, A., Hosking, B., Orsenigo, F., Wilhelm, D., Browne, C., Paavonen, K., Karnezis, T., Shayan, R., Downes, M., Davidson, T., Tutt, D., Cheah, K.S., Stacker, S.A., Muscat, G.E., Achen, M.G., Dejana, E., Koopman, P., 2008. Sox18 induces development of the lymphatic vasculature in mice. Nature 456, 643-647.
Gore, A.V., Swift, M.R., Cha, Y.R., Lo, B., McKinney, M.C., Li, W., Castranova, D., Davis, A., Mukouyama, Y.S., Weinstein, B.M., 2011. Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3. Development 138, 4875-4886.
Hogan, B.M., Bos, F.L., Bussmann, J., Witte, M., Chi, N.C., Duckers, H.J., Schulte-Merker, S., 2009. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet 41, 396-398.
Hong, Y.K., Harvey, N., Noh, Y.H., Schacht, V., Hirakawa, S., Detmar, M., Oliver, G., 2002. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn 225, 351-357.
Jurisic, G., Detmar, M., 2009. Lymphatic endothelium in health and disease. Cell Tissue Res 335, 97-108.
Karkkainen, M.J., Haiko, P., Sainio, K., Partanen, J., Taipale, J., Petrova, T.V., Jeltsch, M., Jackson, D.G., Talikka, M., Rauvala, H., Betsholtz, C., Alitalo, K., 2004. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5, 74-80.
Karkkainen, M.J., Saaristo, A., Jussila, L., Karila, K.A., Lawrence, E.C., Pajusola, K., Bueler, H., Eichmann, A., Kauppinen, R., Kettunen, M.I., Yla-Herttuala, S., Finegold, D.N., Ferrell, R.E., Alitalo, K., 2001. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci U S A 98, 12677-12682.
Karpanen, T., Heckman, C.A., Keskitalo, S., Jeltsch, M., Ollila, H., Neufeld, G., Tamagnone, L., Alitalo, K., 2006. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J 20, 1462-1472.
Kuchler, A.M., Gjini, E., Peterson-Maduro, J., Cancilla, B., Wolburg, H., Schulte-Merker, S., 2006. Development of the zebrafish lymphatic system requires VEGFC signaling. Curr Biol 16, 1244-1248.
Lee, S.J., Chan, T.H., Chen, T.C., Liao, B.K., Hwang, P.P., Lee, H., 2008. LPA1 is essential for lymphatic vessel development in zebrafish. FASEB J 22, 3706-3715.
Lin, C.I., Chen, C.N., Huang, M.T., Lee, S.J., Lin, C.H., Chang, C.C., Lee, H., 2008a. Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells. Cell Mol Life Sci 65, 2740-2751.
Lin, C.I., Chen, C.N., Huang, M.T., Lee, S.J., Lin, C.H., Chang, C.C., Lee, H., 2008b. Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappaB activation- and EGFR transactivation-dependent mechanisms. Cell Signal 20, 1804-1814.
Lin, C.I., Chen, C.N., Lin, P.W., Chang, K.J., Hsieh, F.J., Lee, H., 2007. Lysophosphatidic acid regulates inflammation-related genes in human endothelial cells through LPA1 and LPA3. Biochem Biophys Res Commun 363, 1001-1008.
Liu, S., Umezu-Goto, M., Murph, M., Lu, Y., Liu, W., Zhang, F., Yu, S., Stephens, L.C., Cui, X., Murrow, G., Coombes, K., Muller, W., Hung, M.C., Perou, C.M., Lee, A.V., Fang, X., Mills, G.B., 2009. Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases. Cancer Cell 15, 539-550.
Moolenaar, W.H., 1999. Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res 253, 230-238.
Oliver, G., 2004. Lymphatic vasculature development. Nat Rev Immunol 4, 35-45.
Petrova, T.V., Makinen, T., Makela, T.P., Saarela, J., Virtanen, I., Ferrell, R.E., Finegold, D.N., Kerjaschki, D., Yla-Herttuala, S., Alitalo, K., 2002. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J 21, 4593-4599.
Srinivasan, R.S., Dillard, M.E., Lagutin, O.V., Lin, F.J., Tsai, S., Tsai, M.J., Samokhvalov, I.M., Oliver, G., 2007. Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes Dev 21, 2422-2432.
Su, J.L., Shih, J.Y., Yen, M.L., Jeng, Y.M., Chang, C.C., Hsieh, C.Y., Wei, L.H., Yang, P.C., Kuo, M.L., 2004. Cyclooxygenase-2 induces EP1- and HER-2/Neu-dependent vascular endothelial growth factor-C up-regulation: a novel mechanism of lymphangiogenesis in lung adenocarcinoma. Cancer Res 64, 554-564.
Timoshenko, A.V., Chakraborty, C., Wagner, G.F., Lala, P.K., 2006. COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. Br J Cancer 94, 1154-1163.
Tokumura, A., Majima, E., Kariya, Y., Tominaga, K., Kogure, K., Yasuda, K., Fukuzawa, K., 2002. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 277, 39436-39442.
van Meeteren, L.A., Ruurs, P., Stortelers, C., Bouwman, P., van Rooijen, M.A., Pradere, J.P., Pettit, T.R., Wakelam, M.J., Saulnier-Blache, J.S., Mummery, C.L., Moolenaar, W.H., Jonkers, J., 2006. Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26, 5015-5022.
Wigle, J.T., Harvey, N., Detmar, M., Lagutina, I., Grosveld, G., Gunn, M.D., Jackson, D.G., Oliver, G., 2002. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J 21, 1505-1513.
Yaniv, K., Isogai, S., Castranova, D., Dye, L., Hitomi, J., Weinstein, B.M., 2006. Live imaging of lymphatic development in the zebrafish. Nat Med 12, 711-716.
Yoshida, K., Nishida, W., Hayashi, K., Ohkawa, Y., Ogawa, A., Aoki, J., Arai, H., Sobue, K., 2003. Vascular remodeling induced by naturally occurring unsaturated lysophosphatidic acid in vivo. Circulation 108, 1746-1752.
Yuan, L., Moyon, D., Pardanaud, L., Breant, C., Karkkainen, M.J., Alitalo, K., Eichmann, A., 2002. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 129, 4797-4806.
Yukiura, H., Hama, K., Nakanaga, K., Tanaka, M., Asaoka, Y., Okudaira, S., Arima, N., Inoue, A., Hashimoto, T., Arai, H., Kawahara, A., Nishina, H., Aoki, J., 2011. Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish. J Biol Chem 286, 43972-43983.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65712-
dc.description.abstract水解磷酸酯第一型受體(lysophosphatic acid receptor 1, Lpar1)因其在內皮細胞內之高度表現一直被認為對血管發育有重要影響,然而在其基因剔除小鼠試驗中卻未發現有明顯血管方面的缺陷。本實驗室之前研究中發現弱化lpar1的蛋白質表現會造成斑馬魚胚產生額面軟骨異常,及嚴重的水腫現象。此嚴重的水腫現象來自於淋巴系統發育的異常而導致胸管的消失。因此在本研究中我嘗試分析Lpar1在斑馬魚胚胎發育時的基因表現以及調節淋巴管發育的訊息傳遞路徑。lpar1表現於背大動脈,且與淋巴管發育因子vegfc的表現位置相重疊。抑制lpar1的表現除可抑制胸管形成,還會造成背大動脈與後尾靜脈間的距離短縮。即時聚合酶連鎖反應定量分析顯示vegfc在lpar1表現受抑制的幼魚中有被抑制的現象,而另一可能淋巴管發育因子lyve-1 like則無。Cox2可為LPA所活化,而抑制Cox2之功能亦能發現斑馬魚胸管發育產生缺陷,然而異位表現低劑量的cox2並無法回復此缺陷。綜合以上結果,我認為Lpar1可能經由調控vegfc的表現影響淋巴管新生成,但Lpar1究竟如何調節vegfc的表現有待進一步試驗之證明。zh_TW
dc.description.abstractLysophosphatic acid receptor 1 (Lpar1) has been suggested to have some roles in vascular development because of its high expression in endothelial cells (ECs). However, no significant defect in vascular development was observed in lpar1-knockout mice. We have previously demonstrated that knockdown of lpar1 causes craniofacial cartilage distortion and serious edema in zebrafish. Edema was resulted from the defect in lymphangiogenesis, so I intended to further analyze the expression and regulatory mechanism of Lpar1 in lymphangiogenesis during embryonic development. lpar1 was expressed in dorsal aorta where a lymphatic factor, vegfc, was also expressed. Knockdown of lpar1 caused narrowed space between dorsal aorta and posterior caudal vein. Real-time PCR analysis showed that vegfc but not another lymphatic factor lyve-1 like was reduced in lpar1 morphants. Inhibition of cyclooxygenase-2 (Cox2) caused similar defects in lymphangiogenesis as that in the lpar1 morpholino-injected embryos, but it was unable to be rescued by ectopic expression of cox2 at low dosage. From the results, I suggested that Lpar1 may regulate the expression of vegfc and affect the formation of lymphatic vessels, but its regulatory mechanism remains unclear.en
dc.description.provenanceMade available in DSpace on 2021-06-17T00:00:47Z (GMT). No. of bitstreams: 1
ntu-101-R94b41023-1.pdf: 3394370 bytes, checksum: 591463dc08a5741dba424529bbf27c40 (MD5)
Previous issue date: 2012
en
dc.description.tableofcontentsTable of Content I
List of Figures III
List of Tables IV
中文摘要 1
Abstract 2
Introduction 3
Materials and Methods 6
Fish breeding 6
Sequence analysis 6
RNA isolation 6
Reverse transcription (RT) 7
Polymerase chain reaction (PCR) analysis 7
Plasmid construction 8
Whole-mount in situ hybridization (ISH) 8
Cryosection 9
Microinjection 9
Alcian staining 10
NS398 soaking 10
Realtime PCR analysis 11
Cell dissociation 11
Results 12
Cloning and sequence analysis of zebrafish lpar1 12
Expression analysis of lpar1 13
Knockdown of lpar1 causes craniofacial distortion and defect in lymphangiogenesis 13
Inhibition of cyclooxygenase-2 (Cox2) mimics lpar1-knockdown morphology 15
vegfc and its receptor flt4 are down-regulated in lpar1 morphant 16
Discussion 18
References 22
dc.language.isoen
dc.subject淋巴zh_TW
dc.subject斑馬魚zh_TW
dc.subject發生zh_TW
dc.subjectlymphen
dc.subjectdevelopmenten
dc.subjectzebrafishen
dc.titleLpar1經由Vegfc/Vegfr-3調控斑馬魚淋巴管新生成zh_TW
dc.titleLpar1 regulates lymphangiogenesis through Vegfc/Vegfr-3 in zebrafishen
dc.typeThesis
dc.date.schoolyear100-2
dc.description.degree碩士
dc.contributor.oralexamcommittee陳瑞芬,黃偉邦
dc.subject.keyword淋巴,斑馬魚,發生,zh_TW
dc.subject.keywordlymph,zebrafish,development,en
dc.relation.page40
dc.rights.note有償授權
dc.date.accepted2012-07-16
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

文件中的檔案:
檔案 大小格式 
ntu-101-1.pdf
  未授權公開取用
3.31 MBAdobe PDF
顯示文件簡單紀錄


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。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved