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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 余明俊(Ming-Jiun Yu) | |
dc.contributor.author | Chia-Ching Ma | en |
dc.contributor.author | 馬家慶 | zh_TW |
dc.date.accessioned | 2021-06-16T10:34:27Z | - |
dc.date.available | 2018-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-14 | |
dc.identifier.citation | 1. Van Ree, J.M., et al., Vasopressin and related peptides: animal and human studies. Prog Neuropsychopharmacol Biol Psychiatry, 1985. 9(5-6): p. 551-9.
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Schenk, L.K., et al., Quantitative proteomics identifies vasopressin-responsive nuclear proteins in collecting duct cells. J Am Soc Nephrol, 2012. 23(6): p. 1008-18. 14. Lacorazza, H.D. and S.D. Nimer, The emerging role of the myeloid Elf-1 like transcription factor in hematopoiesis. Blood Cells Mol Dis, 2003. 31(3): p. 342-50. 15. Oettgen, P., et al., Isolation and characterization of a novel epithelium-specific transcription factor, ESE-1, a member of the ets family. Mol Cell Biol, 1997. 17(8): p. 4419-33. 16. Oikawa, T. and T. Yamada, Molecular biology of the Ets family of transcription factors. Gene, 2003. 303: p. 11-34. 17. Sharrocks, A.D., The ETS-domain transcription factor family. Nat Rev Mol Cell Biol, 2001. 2(11): p. 827-37. 18. Otero, M., et al., E74-like factor 3 (ELF3) impacts on matrix metalloproteinase 13 (MMP13) transcriptional control in articular chondrocytes under proinflammatory stress. J Biol Chem, 2012. 287(5): p. 3559-72. 19. Tootle, T.L. and I. Rebay, Post-translational modifications influence transcription factor activity: a view from the ETS superfamily. Bioessays, 2005. 27(3): p. 285-98. 20. Eckel, K.L., et al., The epithelial-specific ETS transcription factor ESX/ESE-1/Elf-3 modulates breast cancer-associated gene expression. DNA Cell Biol, 2003. 22(2): p. 79-94. 21. Wasylyk, B., S.L. Hahn, and A. Giovane, The Ets family of transcription factors. Eur J Biochem, 1993. 211(1-2): p. 7-18. 22. Ng, A.Y., et al., Inactivation of the transcription factor Elf3 in mice results in dysmorphogenesis and altered differentiation of intestinal epithelium. Gastroenterology, 2002. 122(5): p. 1455-66. 23. Tymms, M.J., et al., A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer. Oncogene, 1997. 15(20): p. 2449-62. 24. Fujita, N., et al., Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats. Am J Physiol, 1995. 269(6 Pt 2): p. F926-31. 25. Marples, D., et al., Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex. J Clin Invest, 1996. 97(8): p. 1960-8. 26. Matsumura, Y., et al., Transcriptional regulation of aquaporin-2 water channel gene by cAMP. J Am Soc Nephrol, 1997. 8(6): p. 861-7. 27. Uchida, S., et al., Regulation of aquaporin-2 gene transcription by GATA-3. off. Biochem Biophys Res Commun, 1997. 232(1): p. 65-8. 28. Hasler, U., et al., Tonicity-responsive enhancer binding protein is an essential regulator of aquaporin-2 expression in renal collecting duct principal cells. J Am Soc Nephrol, 2006. 17(6): p. 1521-31. 29. Hasler, U., et al., Aquaporin-2 abundance in the renal collecting duct: new insights from cultured cell models. Am J Physiol Renal Physiol, 2009. 297(1): p. F10-8. 30. Saito, T., et al., Role of aquaporin-2 gene expression in hyponatremic rats with chronic vasopressin-induced antidiuresis. Kidney Int, 2001. 60(4): p. 1266-76. 31. Pisitkun, T., et al., Akt and ERK1/2 pathways are components of the vasopressin signaling network in rat native IMCD. Am J Physiol Renal Physiol, 2008. 295(4): p. F1030-43. 32. Furuno, M., et al., Repressive regulation of the aquaporin-2 gene. Am J Physiol, 1996. 271(4 Pt 2): p. F854-60. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60879 | - |
dc.description.abstract | 抗利尿激素(AVP)是一種多胜肽賀爾蒙,當其從腦下垂體釋放到血液中時, AVP會經由腎臟集尿管來調控尿液中水分的排出,藉此穩定體內水分的平衡。AVP其主要是透過增加集尿管細胞內水通道蛋白2號(aquaporin 2, AQP2)基因的轉錄及轉譯,來增加集尿管細胞對於水的通透性,藉此減少尿液中水分的排出。當AVP無法正常地誘導AQP2基因表現時,會造成一些和身體水分平衡相關的疾病;然而AVP是透過怎樣的分子機制去調控AQP2基因的轉錄,仍然是不清楚的。最近microarray和proteomic的研究指出,轉錄因子Elf1以及Elf3可能參與在AVP所誘導的AQP2基因轉錄的機制當中,因此在我的研究中,想利用小鼠集尿管細胞的細胞株(mpkCCD),來研究轉錄因子Elf1和Elf3是否參與在AVP所誘導的AQP2基因表現的機制當中。由即時聚合酶鏈鎖反應的實驗結果知道當mpkCCD細胞受到抗利尿激素類似物dDAVP的刺激之下, AQP2 mRNA的表現量,會隨著dDAVP刺激的時間增長,而有逐漸增加的趨勢。利用shRNA將mpkCCD細胞中的Elf1以及Elf3進行knockdown,由即時聚合酶鏈鎖反應的分析結果得知,不管是在Elf1或是Elf3 knockdown的細胞當中,其dDAVP所誘導AQP2 mRNA的表現量,都較控制組細胞來的低,尤其在Elf3 knockdown的細胞中, AQP2 mRNA的下降是更為明顯。進一步利用西方點墨法的分析,觀察到mpkCCD細胞Elf3的knockdown,會顯著性降低細胞內dDAVP所誘導的AQP2蛋白質的表現量。由反轉錄聚合酶連鎖反應的分析,看到在mpkCCD細胞當中, Elf3有兩種isoform的表現,分別在mpkCCD細胞中表現這兩種Elf3的isoform,都會造成細胞內dDAVP所誘導的AQP2 mRNA的表現量增加,以及增強AQP2基因啟動子的活性。總結上述的結果,在我的研究中發現,轉錄因子Elf3參與在抗利尿激素所誘導AQP2基因表現的機制當中,並且扮演著正向調控者的角色。 | zh_TW |
dc.description.abstract | Released from the pituitary, vasopressin (AVP) is a peptide hormone that regulates renal water excretion by the collecting ducts. AVP increases transcription and translation levels of the molecular water channel protein aquaporin-2 (AQP2) gene to increase water permeability of the collecting ducts thereby decreasing water excretion. Dysregulation of AQP2 gene expression induced by AVP is associated with many water balance diseases; however the molecular mechanism by which vasopressin regulates AQP2 gene transcription is poorly understood. Several recent microarray and proteomic studies have alluded to potential roles of the ETS-like transcription factor Elf1 and Elf3 in vasopressin-mediated AQP2 transcription. The goal of my study was to investigate whether the transcription factor Elf1 and Elf3 are involved in the regulation of vasopressin-mediated AQP2 gene expression in a mouse collecting duct cell model (mpkCCD). Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the vasopressin analog dDAVP induced AQP2 mRNA expression in a time-dependent manner in mpkCCD cells. Either stable Elf1 knockdown or Elf3 knockdown significantly reduced dDAVP-induced and basic AQP2 mRNA expression, but Elf3 knockdown reduced more AQP2 mRNA production than Elf1 knockdown. Immunoblotting analysis showed that Elf3 knockdown also decreased dDAVP-induced AQP2 protein expression. Furthermore, qRT-PCR and promoter reporter assay revealed that overexpression of either Elf3 isoform 1 or isoform 2 increased AQP2 mRNA levels and promoter activity in the presence and the absence of dDAVP. Collectively, my study shows that transcription factor Elf3 mediates vasopressin-induced and basal AQP2 expression in the mpkCCD cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T10:34:27Z (GMT). No. of bitstreams: 1 ntu-102-R00442021-1.pdf: 4072924 bytes, checksum: 006aa2a87b763a001c7af87bdc9ece7e (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 誌謝 I
摘要 III Abstract IV Chapter 1. Introduction 1 Chapter 2. Materials 6 Chapter 3. Methods 12 Chapter 4. Results 27 The vasopressin analog dDAVP stimulated AQP2 mRNA and protein expression in the mpkCCD cells. 28 Elf1 knockdown decreased AQP2 mRNA levels in the absence and presence of vasopressin. 29 Elf3 knockdown decreased AQP2 mRNA levels in the absence and presence of vasopressin. 30 Elf3 knockdown decreased AQP2 protein levels in the presence of vasopressin. 31 Overexpression of either Elf3 isoform 1 or isoform 2 increased AQP2 mRNA levels and promoter activity in the absence and presence of vasopressin. 32 Either Elf3 isoform 1 or isoform 2 binds AQP2 promoter sequence from -444 to -416. 33 Chapter 5. Discussion 34 Chapter 6. Figures and Legends 39 Chapter 7. References 49 | |
dc.language.iso | en | |
dc.title | 轉錄因子Elf3參與抗利尿激素所誘導的水通道蛋白2號基因之表現 | zh_TW |
dc.title | Transcription Factor Elf3 Mediates Vasopressin-Regulated Aquaporin-2 Expression in mpkCCD Cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 孫錦虹,繆希椿 | |
dc.subject.keyword | 抗利尿激素,水通道蛋白2號,腎臟集尿管細胞,轉錄因子Elf1,Elf3, | zh_TW |
dc.subject.keyword | Vasopressin,aquaporin 2,renal collecting duct cells,Elf1,Elf3, | en |
dc.relation.page | 52 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-14 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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