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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蕭信宏 | |
| dc.contributor.author | Jiun-Yuan Wang | en |
| dc.contributor.author | 王俊淵 | zh_TW |
| dc.date.accessioned | 2021-06-07T17:59:21Z | - |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-08 | |
| dc.identifier.citation | Anderson KV, Nusslein-Volhard C: Information for the dorsal--ventral pattern of the Drosophila embryo is stored as maternal mRNA. Nature 1984, 311(5983):223-227.
Angerer L, Hussain S, Wei Z, Livingston BT: Sea urchin metalloproteases: a genomic survey of the BMP-1/tolloid-like, MMP and ADAM families. Dev Biol 2006, 300(1):267-281. Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C et al: Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1999, 1(5):260-266. Attardo GM, Hansen IA, Raikhel AS: Nutritional regulation of vitellogenesis in mosquitoes: implications for anautogeny. Insect Biochem Mol Biol 2005, 35(7):661-675. Attardo GM, Hansen IA, Shiao SH, Raikhel AS: Identification of two cationic amino acid transporters required for nutritional signaling during mosquito reproduction. J Exp Biol 2006, 209(Pt 16):3071-3078. Attardo GM, Higgs S, Klingler KA, Vanlandingham DL, Raikhel AS: RNA interference-mediated knockdown of a GATA factor reveals a link to anautogeny in the mosquito Aedes aegypti. Proc Natl Acad Sci U S A 2003, 100(23):13374-13379. Beaucher M, Goodliffe J, Hersperger E, Trunova S, Frydman H, Shearn A: Drosophila brain tumor metastases express both neuronal and glial cell type markers. Dev Biol 2007, 301(1):287-297. Beaucher M, Hersperger E, Page-McCaw A, Shearn A: Metastatic ability of Drosophila tumors depends on MMP activity. Dev Biol 2007, 303(2):625-634. Behrens J: Cross-regulation of the Wnt signalling pathway: a role of MAP kinases. J Cell Sci 2000, 113 ( Pt 6):911-919. Bischoff V, Vignal C, Boneca IG, Michel T, Hoffmann JA, Royet J: Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol 2004, 5(11):1175-1180. Bode W, Gomis-Ruth FX, Stockler W: Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'. FEBS Lett 1993, 331(1-2):134-140. Boutros M, Agaisse H, Perrimon N: Sequential activation of signaling pathways during innate immune responses in Drosophila. Dev Cell 2002, 3(5):711-722. Bownes M: Expression of the genes coding for vitellogenin(yolk protein). Ann Rev Entomol 1986:31,507-531. . Brinckerhoff CE, Matrisian LM: Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 2002, 3(3):207-214. Brown MR, Graf R, Swiderek KM, Fendley D, Stracker TH, Champagne DE, Lea AO: Identification of a steroidogenic neurohormone in female mosquitoes. J Biol Chem 1998, 273(7):3967-3971. Brumby AM, Richardson HE: scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J 2003, 22(21):5769-5779. Carpenter VK, Drake LL, Aguirre SE, Price DP, Rodriguez SD, Hansen IA: SLC7 amino acid transporters of the yellow fever mosquito Aedes aegypti and their role in fat body TOR signaling and reproduction. J Insect Physiol 2012. Chen LH, Wilson ME: Dengue and chikungunya infections in travelers. Current Opinion in Infectious Diseases 2010, 23(5):438-444. Coates D, Siviter R, Isaac RE: Exploring the Caenorhabditis elegans and Drosophila melanogaster genomes to understand neuropeptide and peptidase function. Biochem Soc Trans 2000, 28(4):464-469. Colombani J, Raisin S, Pantalacci S, Radimerski T, Montagne J, Leopold P: A nutrient sensor mechanism controls Drosophila growth. Cell 2003, 114(6):739-749. Cooper TG: Transmitting the signal of excess nitrogen in Saccharomyces cerevisiae from the Tor proteins to the GATA factors: connecting the dots. FEMS Microbiol Rev 2002, 26(3):223-238. Costa A, Jan E, Sarnow P, Schneider D: The Imd pathway is involved in antiviral immune responses in Drosophila. PLoS One 2009, 4(10):e7436. Coussens LM, Fingleton B, Matrisian LM: Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002, 295(5564):2387-2392. Deitsch KW, Chen JS, Raikhel AS: Indirect control of yolk protein genes by 20-hydroxyecdysone in the fat body of the mosquito, Aedes aegypti. Insect Biochem Mol Biol 1995, 25(4):449-454. Delaney JR, Mlodzik M: TGF-beta activated kinase-1: new insights into the diverse roles of TAK1 in development and immunity. Cell Cycle 2006, 5(24):2852-2855. Dunker N, Krieglstein K: Targeted mutations of transforming growth factor-beta genes reveal important roles in mouse development and adult homeostasis. Eur J Biochem 2000, 267(24):6982-6988. Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002, 2(3):161-174. Farina AR, Coppa A, Tiberio A, Tacconelli A, Turco A, Colletta G, Gulino A, Mackay AR: Transforming growth factor-beta1 enhances the invasiveness of human MDA-MB-231 breast cancer cells by up-regulating urokinase activity. Int J Cancer 1998, 75(5):721-730. Fong YL, Cadigan FC, Coatney GR: A presumptive case of naturally occurring Plasmodium knowlesi malaria in man in Malaysia. Trans R Soc Trop Med Hyg 1971, 65(6):839-840. Fradin MS: Mosquitoes and mosquito repellents: a clinician's guide. Ann Intern Med 1998, 128(11):931-940. Geoffrey M. Attardo, Immo A. Hansen, Shiao S-H, Raikhel AS: Identification of two cationic amino acid transporters required for nutritional signaling during mosquito reproduction. 2006. Ghosh D, Basu A: Japanese encephalitis-a pathological and clinical perspective. PLoS Negl Trop Dis 2009, 3(9):e437. Godenschwege TA, Pohar N, Buchner S, Buchner E: Inflated wings, tissue autolysis and early death in tissue inhibitor of metalloproteinases mutants of Drosophila. Eur J Cell Biol 2000, 79(7):495-501. Golldack D, Popova OV, Dietz KJ: Mutation of the matrix metalloproteinase At2-MMP inhibits growth and causes late flowering and early senescence in Arabidopsis. J Biol Chem 2002, 277(7):5541-5547. Gottar M, Gobert V, Matskevich AA, Reichhart JM, Wang C, Butt TM, Belvin M, Hoffmann JA, Ferrandon D: Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell 2006, 127(7):1425-1437. Gross J, Lapiere CM: Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci U S A 1962, 48:1014-1022. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martinez E et al: Dengue: a continuing global threat. Nat Rev Microbiol 2010, 8(12 Suppl):S7-16. Hagedorn HH: The role of ecdysteroids in reproduction. In: Kerkut, G., Gilbert, L.(Eds.), Comprehensive Insect Physiology. Biochemistry and Pharmacology 1985:8, 205-261. . Hagedorn HH: Physiological roles of hemolymph ecdysteroid in the adult insect. In: Koolman, J.(Ed.), Ecdysone from Chemistry to Mode of Action. . New York, Thieme Medical Publishers, 1989: Inc, 79-289 Hansen IA, Attardo GM, Park JH, Peng Q, Raikhel AS: Target of rapamycin-mediated amino acid signaling in mosquito anautogeny. Proc Natl Acad Sci U S A 2004, 101(29):10626-10631. Hansen IA, Attardo GM, Roy SG, Raikhel AS: Target of rapamycin-dependent activation of S6 kinase is a central step in the transduction of nutritional signals during egg development in a mosquito. J Biol Chem 2005, 280(21):20565-20572. Heitman J, Movva NR, Hiestand PC, Hall MN: FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 1991, 88(5):1948-1952. Hoffmann JA, Kafatos FC, Janeway CA, Ezekowitz RA: Phylogenetic perspectives in innate immunity. Science 1999, 284(5418):1313-1318. Janji B, Melchior C, Gouon V, Vallar L, Kieffer N: Autocrine TGF-beta-regulated expression of adhesion receptors and integrin-linked kinase in HT-144 melanoma cells correlates with their metastatic phenotype. Int J Cancer 1999, 83(2):255-262. Johansson N, Ala-aho R, Uitto V, Grenman R, Fusenig NE, Lopez-Otin C, Kahari VM: Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase. J Cell Sci 2000, 113 Pt 2:227-235. Khush RS, Leulier F, Lemaitre B: Drosophila immunity: two paths to NF-kappaB. Trends Immunol 2001, 22(5):260-264. Kiger JA, Jr., Natzle JE, Kimbrell DA, Paddy MR, Kleinhesselink K, Green MM: Tissue remodeling during maturation of the Drosophila wing. Dev Biol 2007, 301(1):178-191. Kim J, Guan KL: Amino acid signaling in TOR activation. Annu Rev Biochem 2011, 80:1001-1032. Kim T, Kim YJ: Overview of innate immunity in Drosophila. J Biochem Mol Biol 2005, 38(2):121-127. Kokoza VA, Martin D, Mienaltowski MJ, Ahmed A, Morton CM, Raikhel AS: Transcriptional regulation of the mosquito vitellogenin gene via a blood meal-triggered cascade. Gene 2001, 274(1-2):47-65. Kuo CT, Jan LY, Jan YN: Dendrite-specific remodeling of Drosophila sensory neurons requires matrix metalloproteases, ubiquitin-proteasome, and ecdysone signaling. Proc Natl Acad Sci U S A 2005, 102(42):15230-15235. Kurata S: Extracellular and intracellular pathogen recognition by Drosophila PGRP-LE and PGRP-LC. International Immunology 2010, 22(3):143-148. Lea AO: The medial neurosecretory cells and egg maturation in mosquitoes. J Insect Physiol 1967, 13(3):419-429. Lemaitre B, Hoffmann J: The host defense of Drosophila melanogaster. Annu Rev Immunol 2007, 25:697-743. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA: The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996, 86(6):973-983. Leontovich AA, Zhang J, Shimokawa K, Nagase H, Sarras MP, Jr.: A novel hydra matrix metalloproteinase (HMMP) functions in extracellular matrix degradation, morphogenesis and the maintenance of differentiated cells in the foot process. Development 2000, 127(4):907-920. Levashina EA, Langley E, Green C, Gubb D, Ashburner M, Hoffmann JA, Reichhart JM: Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila. Science 1999, 285(5435):1917-1919. Li C, Kapitskaya MZ, Zhu J, Miura K, Segraves W, Raikhel AS: Conserved molecular mechanism for the stage specificity of the mosquito vitellogenic response to ecdysone. Dev Biol 2000, 224(1):96-110. Liu Z, Li N, Diaz LA, Shipley M, Senior RM, Werb Z: Synergy between a plasminogen cascade and MMP-9 in autoimmune disease. J Clin Invest 2005, 115(4):879-887. Llano E, Pendas AM, Aza-Blanc P, Kornberg TB, Lopez-Otin C: Dm1-MMP, a matrix metalloproteinase from Drosophila with a potential role in extracellular matrix remodeling during neural development. J Biol Chem 2000, 275(46):35978-35985. Lynch CJ, Fox HL, Vary TC, Jefferson LS, Kimball SR: Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes. J Cell Biochem 2000, 77(2):234-251. Maidment JM, Moore D, Murphy GP, Murphy G, Clark IM: Matrix metalloproteinase homologues from Arabidopsis thaliana. Expression and activity. J Biol Chem 1999, 274(49):34706-34710. Martin D, Piulachs MD, Raikhel AS: A novel GATA factor transcriptionally represses yolk protein precursor genes in the mosquito Aedes aegypti via interaction with the CtBP corepressor. Mol Cell Biol 2001, 21(1):164-174. McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM: Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 2000, 289(5482):1202-1206. Michel T, Reichhart JM, Hoffmann JA, Royet J: Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 2001, 414(6865):756-759. Mihaly J, Kockel L, Gaengel K, Weber U, Bohmann D, Mlodzik M: The role of the Drosophila TAK homologue dTAK during development. Mech Dev 2001, 102(1-2):67-79. Monath TP: Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A 1994, 91(7):2395-2400. Overall CM: Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. Mol Biotechnol 2002, 22(1):51-86. Page-McCaw A, Ewald AJ, Werb Z: Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 2007, 8(3):221-233. Page-McCaw A, Serano J, Sante JM, Rubin GM: Drosophila matrix metalloproteinases are required for tissue remodeling, but not embryonic development. Dev Cell 2003, 4(1):95-106. Pal S, Wu LP: Pattern recognition receptors in the fly Lessons we can learn from the Drosophila melanogaster immune system. Fly 2009, 3(2):121-129. Park JH, Attardo GM, Hansen IA, Raikhel AS: GATA factor translation is the final downstream step in the amino acid/target-of-rapamycin-mediated vitellogenin gene expression in the anautogenous mosquito Aedes aegypti. J Biol Chem 2006, 281(16):11167-11176. Park JM, Brady H, Ruocco MG, Sun H, Williams D, Lee SJ, Kato T, Jr., Richards N, Chan K, Mercurio F et al: Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila. Genes Dev 2004, 18(5):584-594. Raikhel AS, Miura, K., Segraves, W.A. : Nuclear receptors in mosquito vitellogenesis. Amer Zoologist 1999: 39(34),722-735. . Raikhel AS: Vitellogenesis in the mosquitoes. In: Advances in Disease Vector Reach Springer, New York 1992:PP 1-39. Raikhel AS DK, Sappungton TW. In: Crampton JM, Bread CB, Louis C. (Eds): cell and organ culture: culture and analysis of insect fatbody. The Moleculer Biology of insect Disease Vector: A Method Manual Chapman & Hall, London 1997:pp. 507-522. Ranjit S, Kissoon N: Dengue hemorrhagic fever and shock syndromes. Pediatr Crit Care Med 2011, 12(1):90-100. Reiter P: Yellow fever and dengue: a threat to Europe? Euro Surveill 2010, 15(10):19509. Roubaud E: Cycle autogene d'attente et generations hivernales suractives inapparentes chez le moustique commun Culex pipiens. C R Acad Sci 1929:735-738. Roy SG, Raikhel AS: Nutritional and hormonal regulation of the TOR effector 4E-binding protein (4E-BP) in the mosquito Aedes aegypti. FASEB J 2012, 26(3):1334-1342. Ryu JH, Ha EM, Lee WJ: Innate immunity and gut-microbe mutualism in Drosophila. Developmental and Comparative Immunology 2010, 34(4):369-376. Safina A, Ren MQ, Vandette E, Bakin AV: TAK1 is required for TGF-beta 1-mediated regulation of matrix metalloproteinase-9 and metastasis. Oncogene 2008, 27(9):1198-1207. Saurabh G. Roy, Raikhel AS: The small GTPase Rheb is a key component linking amino acid signaling and TOR in the nutritional pathway that controls mosquito egg development. 2011. Shibuya H, Iwata H, Masuyama N, Gotoh Y, Yamaguchi K, Irie K, Matsumoto K, Nishida E, Ueno N: Role of TAK1 and TAB1 in BMP signaling in early Xenopus development. EMBO J 1998, 17(4):1019-1028. Shim JH, Xiao C, Paschal AE, Bailey ST, Rao P, Hayden MS, Lee KY, Bussey C, Steckel M, Tanaka N et al: TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev 2005, 19(22):2668-2681. Shimizu H, Zhang X, Zhang J, Leontovich A, Fei K, Yan L, Sarras MP, Jr.: Epithelial morphogenesis in hydra requires de novo expression of extracellular matrix components and matrix metalloproteinases. Development 2002, 129(6):1521-1532. Silverman N, Maniatis T: NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev 2001, 15(18):2321-2342. Silverman N, Zhou R, Erlich RL, Hunter M, Bernstein E, Schneider D, Maniatis T: Immune activation of NF-kappaB and JNK requires Drosophila TAK1. J Biol Chem 2003, 278(49):48928-48934. Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, Thomas A, Conway DJ: A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004, 363(9414):1017-1024. Srivastava A, Pastor-Pareja JC, Igaki T, Pagliarini R, Xu T: Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion. Proc Natl Acad Sci U S A 2007, 104(8):2721-2726. Stocker W, Grams F, Baumann U, Reinemer P, Gomis-Ruth FX, McKay DB, Bode W: The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases. Protein Sci 1995, 4(5):823-840. Suarez-Cuervo C, Merrell MA, Watson L, Harris KW, Rosenthal EL, Vaananen HK, Selander KS: Breast cancer cells with inhibition of p38alpha have decreased MMP-9 activity and exhibit decreased bone metastasis in mice. Clin Exp Metastasis 2004, 21(6):525-533. Sutherland CJ, Tanomsing N, Nolder D, Oguike M, Jennison C, Pukrittayakamee S, Dolecek C, Hien TT, do Rosario VE, Arez AP et al: Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally. J Infect Dis 2010, 201(10):1544-1550. Takatsu Y, Nakamura M, Stapleton M, Danos MC, Matsumoto K, O'Connor MB, Shibuya H, Ueno N: TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development. Mol Cell Biol 2000, 20(9):3015-3026. Tolle MA: Mosquito-borne diseases. Curr Probl Pediatr Adolesc Health Care 2009, 39(4):97-140. Trampuz A, Jereb M, Muzlovic I, Prabhu RM: Clinical review: Severe malaria. Crit Care 2003, 7(4):315-323. Uhlirova M, Bohmann D: JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. EMBO J 2006, 25(22):5294-5304. Varatharaj A: Encephalitis in the clinical spectrum of dengue infection. Neurol India 2010, 58(4):585-591. Vezina C, Kudelski A, Sehgal SN: Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo) 1975, 28(10):721-726. Wada K, Sato H, Kinoh H, Kajita M, Yamamoto H, Seiki M: Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases. Gene 1998, 211(1):57-62. Wang SF, Li C, Sun G, Zhu J, Raikhel AS: Differential expression and regulation by 20-hydroxyecdysone of mosquito ecdysteroid receptor isoforms A and B. Mol Cell Endocrinol 2002, 196(1-2):29-42. Whitehorn J, Farrar J: Dengue. Br Med Bull 2010, 95:161-173. Xi Z, Ramirez JL, Dimopoulos G: The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 2008, 4(7):e1000098. Xu T, Rubin GM: Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 1993, 117(4):1223-1237. Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K: Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science 1995, 270(5244):2008-2011. Zhu J, Chen L, Raikhel AS: Posttranscriptional control of the competence factor betaFTZ-F1 by juvenile hormone in the mosquito Aedes aegypti. Proc Natl Acad Sci U S A 2003, 100(23):13338-13343. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16052 | - |
| dc.description.abstract | 蚊子會造成許多不同傳染病之傳播，其主要為瘧疾、登革熱、黃熱病、日本腦炎與絲蟲病等疾病傳播之媒介。由於一直以來針對這些熱帶疾病所使用之疫苗或治療藥物相當缺乏，並且亦會有抗藥性的產生，因此發展有效控制病媒蚊疾病傳播之替代方法則為現今相當重要的課題。過去研究已知，在果蠅(Drosophila)系統中之Toll pathway與Immune deficiency (IMD) pathway主要負責調控果蠅抗菌胜肽的產生，其中Toll pathway在果蠅受到革蘭氏陽性菌或真菌感染時會啟動，而當果蠅受到革蘭氏陰性菌感染時則會啟動IMD pathway。除了調控免疫反應之外，屬於IMD pathway 下游且受到transforming growth factor-β-activated kinase1 (TAK1)調控之JNK pathway，其主要功能為控制果蠅發育過程中tissue remodeling作用。此外，過去研究發現MMP1 (Matrix Metalloprotienase 1) 亦會參與調控果蠅胚胎之tissue remodeling過程。本實驗室之前研究發現，埃及斑蚊之TAK1 (AaTAK1) 基因亦會調控埃及斑蚊受到革蘭氏陽性菌刺激時抗菌胜肽Cecropin A的表現，此外亦發現埃及斑蚊MMP1(AaMMP1)會影響埃及斑蚊吸血之後卵黃生成 (Vitellogenesis) 作用。我們利用RNA干擾方式抑制埃及斑蚊TAK1之表達，發現MMP1之轉譯層次的表達會受到抑制。因此本研究主要想要探討在埃及斑蚊中IMD pathway調控MMP1基因表現的分子機制為何。首先我們利用即時定量PCR (quantitative real-time PCR) 之方式探討AaTAK1轉錄層次之表現情形 (expression pattern)，我們觀察到AaTAK1之mRNA在埃及斑蚊吸血之後12小時到72小時會有大量表現的情形，且主要表現在埃及斑蚊之卵巢與中腸; 接著我我們利用抑制AaTAK1之表現的方式進一步研究AaTAK1之功能，透過利用顯微注射的方式將我們針對AaTAK1部分片段設計的雙股RNA (double-stranded RNA) 注射進入母蚊體內，再進一步進行功能分析。結果發現，當利用RNA干擾方式抑制AaTAK1表現時，埃及斑蚊之母蚊產卵量 (egg production) 會有下降的趨勢 ; 接著我們利用in vitro fat body culture的方式進行實驗，我們發現若利用RNA interference的方式抑制AaTAK1表現或利用AaJNK抑制劑 (SP600125) 抑制AaJNK表現的狀況下，皆會使Vitellogenin (Vg)表現受到抑制，此外，當AaJNK表現受到RNA 干擾方式抑制時，母蚊之產卵量亦會下降。當透過直接注射雙股RNA進入母蚊方式抑制AaTAK1與AaJNK表現時，則可造成母蚊之脂肪體中TOR pathway下游之S6K磷酸化反應受到抑制，並且更進一步發現受到TOR pathway 調控之Vitellogenin (Vg)與AaMMP1表現量亦會減少。總而言之，我們證明AaTAK1與AaJNK在埃及斑蚊之卵黃發育的過程中扮演相當重要的角色，並且其可能是透過調控TOR pathway之活化，再進一步影響AaMMP1之表現與卵黃生成之能力。 | zh_TW |
| dc.description.abstract | Mosquitoes transmit several devastating infectious disease such as malaria, dengue fever, yellow fever, Japanese encephalitis and filariasis. Due to the lack of effective vaccine and the increasing drug and insecticide resistance, alternative approaches for these vector-borne disease are urgently required. It has been demonstrated that the Toll and the Immune Deficiency (IMD) signaling pathways play crucial roles in the production of antimicrobial peptides in the Drosophila. Toll pathway was primarily activated by the stimulation of Gram-positive bacteria or fungi, whereas IMD pathway was responsive to the challenge of Gram-negative bacteria. On the other hand, Matrix metalloproteinase 1 (MMP1) was demonstrated to be essential for the embryonic development in the Drosophila and JNK pathway was shown to be activated by transforming growth factor-β-activated kinase 1 (TAK1), the component of IMD pathway, and to play an important role in tissue modeling in Drosophila. Our previous study showed that Aedes aegypti TAK1 (AaTAK1) is responsible for the production of Cecropin A. We also showed the novel role of Aedes aegypti Matrix metalloproteinase 1 (AaMMP1) in the regulation of vitellogenesis. Our preliminary data revealed that silence of AaTAK1 by RNA interference approach resulted in the inhibition of AaMMP1 in the translational level. In this study, we will elucidate the molecular mechanism in the regulation of AaMMP1 by IMD pathway. We showed that the transcriptional pattern of AaTAK1 is highly expressed from 12 to 72 hours after a blood meal and particularly in the ovary and midgut. By RNAi-mediated silencing of AaTAK1, we showed that the egg production was reduced in the absence of AaTAK1. Interestingly, the expression of Vitellogenin (Vg) was inhibited in the absence of AaTAK1 or with the application of JNK inhibitor (SP600125) in the in vitro fat body culture system. In addition, by RNAi mediated silencing of AaJNK, the egg production was also reduced. Furthermore, we showed that silencing of AaTAK1 or AaJNK inhibit the phosphorylation of S6K, a key component of TOR pathway, and also inhibit the expression of Vitellogenin (Vg) and AaMMP1 in the fat body. Taken together, our data suggest a novel function of AaTAK1 and AaJNK in the regulation of vitellogenesis and AaMMP1 through TOR signaling pathway. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T17:59:21Z (GMT). No. of bitstreams: 1 ntu-101-R99445205-1.pdf: 8680913 bytes, checksum: e24d80afe36c49037ac10b06803f90c0 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 摘要 iii Abstract v 目錄 vii 第一章 緒論(Introduction) 1 1.1 蚊子傳播之疾病 (Mosquito-borne disease) 1 1.1.1登革熱 (Dengue fever) 2 1.1.2 台灣地區登革熱流行病學 3 1.1.3 瘧疾(Malaria) 3 1.2 埃及斑蚊之發育與卵黃生成之調控機制 4 1.3 雙翅目節肢動物之免疫反應 6 1.4 TOR signaling pathway 介紹 8 1.5 Matrix metalloproteinase (MMP)介紹 9 1.6 Transforming growth factor-β activated kinase-1 (TAK1)介紹 12 1.7 實驗目的與研究動機 13 第二章 材料與方法(Methods and Materials) 15 2.1 實驗流程與步驟 15 2.1.1 埃及斑蚊之飼養與繼代 15 2.1.2 肌肉麻醉劑Avertin製備 15 2.1.3 製備double stranded RNA (dsRNA)基本流程 16 2.1.3.1 埃及斑蚊RNA之萃取 16 2.1.3.2 Reverse Transcription(反轉錄作用) 17 2.1.3.3 聚合酶鏈鎖反應 (Polymerase chain reaction, PCR)放大目標基因序列 17 2.1.3.4 質體建構 18 2.1.3.5 dsRNA合成與純化 19 2.1.4 Gene knock-down之方法與 knock-down效率測試 19 2.1.5 RT-PCR (Reverse Transcription-Polymerase Chain Reaction) 20 2.1.6 即時定量聚合酶鏈鎖反應 (Real-time PCR, Quantitative PCR) 21 2.1.7 西方點墨法 (Western blot) 21 2.1.8 產卵實驗 (Egg production assay) 22 2.1.9 In vito fat body culture assay 23 2.1.10 明膠蛋白酵素電泳法 (Gelatin Zymography) 23 2.2 實驗所使用之試劑及配置方式 25 第三章 實驗結果(Results) 27 3.1 埃及斑蚊TAK1基因家族演化分析 27 3.2 埃及斑蚊TAK1 蛋白質序列功能區域預測 27 3.3 埃及斑蚊TAK1於不同發育時期之表現 28 3.4 埃及斑蚊不同組織中TAK1表現情形 28 3.5 埃及斑蚊TAK1對於母蚊產卵之影響 29 3.6 埃及斑蚊JNK對於母蚊產卵之影響 29 3.7 埃及斑蚊TAK1與母蚊卵黃生成之關係 30 3.8 埃及斑蚊JNK與母蚊卵黃生成之關係 30 3.9 埃及斑蚊TAK1及JNK與TOR pathway之調控機制 31 3.10 埃及斑蚊TAK1及JNK對於Vg蛋白質表現之調控 31 3.11埃及斑蚊TAK1對於Vg RNA表現之調控 32 3.12 埃及斑蚊TAK1及 JNK與MMP1之關係 32 3.13 埃及斑蚊MMP1活性啟動時期 33 第四章 討論(Discussion) 34 圖表(Figures) 39 附錄(Appendixes) 54 參考文獻(References) 56 | |
| dc.language.iso | zh-TW | |
| dc.subject | JNK | zh_TW |
| dc.subject | 埃及斑蚊 | zh_TW |
| dc.subject | 卵黃生成 | zh_TW |
| dc.subject | MMP1 | zh_TW |
| dc.subject | TAK1 | zh_TW |
| dc.subject | Aedes aegypti | en |
| dc.subject | JNK | en |
| dc.subject | TAK1 | en |
| dc.subject | MMP1 | en |
| dc.subject | Vitellogenesis | en |
| dc.title | 埃及斑蚊TAK1參與調控基質金屬蛋白酶之功能性研究 | zh_TW |
| dc.title | Functional roles of TAK1 in the regulation of Aedes aegypti matrix metalloproteinase | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 余明俊,李財坤,游偉絢 | |
| dc.subject.keyword | 埃及斑蚊,卵黃生成,MMP1,TAK1,JNK, | zh_TW |
| dc.subject.keyword | Aedes aegypti,Vitellogenesis,MMP1,TAK1,JNK, | en |
| dc.relation.page | 65 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-08-09 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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