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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 | Cheng-Hsuan Ho | en |
dc.contributor.author | 何承軒 | zh_TW |
dc.date.accessioned | 2021-06-17T06:40:37Z | - |
dc.date.available | 2023-09-04 | |
dc.date.copyright | 2018-09-04 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-08-15 | |
dc.identifier.citation | References
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Khurana, S., et al., The actin-binding protein, actinin alpha 4 (ACTN4), is a nuclear receptor coactivator that promotes proliferation of MCF-7 breast cancer cells. J Biol Chem, 2011. 286(3): p. 1850-9. 25. Khurana, S., et al., Identification of a novel LXXLL motif in alpha-actinin 4-spliced isoform that is critical for its interaction with estrogen receptor alpha and co-activators. J Biol Chem, 2012. 287(42): p. 35418-29. 26. Uchida, S., et al., Regulation of aquaporin-2 gene transcription by GATA-3. off. Biochem Biophys Res Commun, 1997. 232(1): p. 65-8. 27. Yasui, M., et al., Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. Am J Physiol, 1997. 272(4 Pt 2): p. F443-50. 28. Yu, M.J., et al., Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct. Proc Natl Acad Sci U S A, 2009. 106(7): p. 2441-6. 29. Hozawa, S., E.J. Holtzman, and D.A. Ausiello, cAMP motifs regulating transcription in the aquaporin 2 gene. Am J Physiol, 1996. 270(6 Pt 1): p. C1695-702. 30. Rai, T., et al., Cloning of rat and mouse aquaporin-2 gene promoters and identification of a negative cis-regulatory element. Am J Physiol, 1997. 273(2 Pt 2): p. F264-73. 31. Chen, M., et al., Dexamethasone increases aquaporin-2 protein expression in ex vivo inner medullary collecting duct suspensions. Front Physiol, 2015. 6: p. 310. 32. Hayashi, R., et al., Effects of glucocorticoids on gene transcription. Eur J Pharmacol, 2004. 500(1-3): p. 51-62. 33. Sever, R. and C.K. Glass, Signaling by nuclear receptors. Cold Spring Harb Perspect Biol, 2013. 5(3): p. a016709. 34. Kumar, R. and E.B. Thompson, Gene regulation by the glucocorticoid receptor: structure:function relationship. J Steroid Biochem Mol Biol, 2005. 94(5): p. 383-94. 35. Zhang, X., et al., Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice. Proc Natl Acad Sci U S A, 2014. 111(6): p. 2277-82. 36. Su, W., et al., Liver X receptor beta increases aquaporin 2 protein level via a posttranscriptional mechanism in renal collecting ducts. Am J Physiol Renal Physiol, 2017. 312(4): p. F619-F628. 37. Zhou, L., et al., Systemic PPARgamma deletion causes severe disturbance in fluid homeostasis in mice. Physiol Genomics, 2015. 47(11): p. 541-7. 38. Evans, L.C., et al., A urine-concentrating defect in 11beta-hydroxysteroid dehydrogenase type 2 null mice. Am J Physiol Renal Physiol, 2012. 303(4): p. F494-502. 39. Cheema, M.U., et al., Estradiol regulates AQP2 expression in the collecting duct: a novel inhibitory role for estrogen receptor alpha. Am J Physiol Renal Physiol, 2015. 309(4): p. F305-17. 40. Jung, H.J., et al., Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPbeta in Vasopressin-Sensitive Collecting Duct Cells. J Am Soc Nephrol, 2018. 29(5): p. 1490-1500. 41. Ramji, D.P. and P. Foka, CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem J, 2002. 365(Pt 3): p. 561-75. 42. Wedel, A. and H.W. Ziegler-Heitbrock, The C/EBP family of transcription factors. Immunobiology, 1995. 193(2-4): p. 171-85. 43. Savoldi, G., et al., The glucocorticoid receptor regulates the binding of C/EPBbeta on the alpha-1-acid glycoprotein promoter in vivo. DNA Cell Biol, 1997. 16(12): p. 1467-76. 44. Boruk, M., J.G. Savory, and R.J. Hache, AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor. Mol Endocrinol, 1998. 12(11): p. 1749-63. 45. Bens, M., et al., Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line. J Am Soc Nephrol, 1999. 10(5): p. 923-34. 46. Baxter, J.D., et al., Tissue effects of glucocorticoids. Am J Med, 1972. 53(5): p. 573-89. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72407 | - |
dc.description.abstract | 抗利尿激素(vasopressin,簡稱AVP)是調控腎臟集尿管水分通透性的多胜肽賀爾蒙。受到AVP刺激的一小時內,會將原本儲存於胞內囊泡的第二型水通道蛋白(aquaporin-2,簡稱AQP2)運送到細胞頂膜(apical membrane),因而增加水分的通透性。受到AVP刺激的數小時到數天內,會增加細胞內AQP2基因表現,調節水分的通透性。上述這兩個受到AVP調控的過程看似不相關。先前研究在集尿管細胞模型(mpkCCD)受到AVP刺激時鑑定到α-actinin 4,一方面,能與肌動單白結合的α-actinin 4參與細胞骨架的動態行為, AQP2的運送過程中也需要細胞骨架的動態行為。另一方面,α-actinin 4也被報導做為許多轉錄因子的轉錄共調控者,其中包括糖皮質激素受體(glucocorticoid receptor,簡稱GR),而GR這個轉錄因子在mpkCCD細胞中也已被暗示會參與在抗利尿激素所誘導的AQP2基因表現中,所以AVP可能透過增加α-actinin 4和GR的交互作用來引發AQP2的基因表現。因此,我們提出了一個假說:α-輔肌動蛋白4 (α-actinin 4)可能將這兩個調控的過程連結在一起。結果顯示:α-actinin 4短髮夾RNA(shRNA)抑制α-actinin 4的基因表現會降低mpkCCD細胞中由抗利尿激素誘導的AQP2 mRNA和蛋白量。α-actinin 4並不影響抗利尿激素誘導AQP2 mRNA的穩定性但會活化AQP2的啟動子而部分地增強了抗利尿激素誘導的AQP2轉錄作用。進一步研究其分子機制,發現:mpkCCD細胞受AVP刺激後會刺激α-actinin 4進入細胞核的作用,並會增加GR在細胞核內的量。當抑制了GR在mpkCCD細胞中的基因表現後由抗利尿激素所誘導的AQP2 mRNA和蛋白量降低了。我們接著利用promoter-reporter assay發現GR增強了由抗利尿激素所誘導的AQP2啟動子活性,GR也會調控AVP V2受體的mRNA量。上述的結果意味著GR在抗利尿激素誘導AQP2的基因表現中發揮了作用。綜上所述,我們的結論是α-actinin 4在腎臟集尿管細胞中擔任GR的轉錄共調控者,進而調控由抗利尿激素誘導的AQP2基因表現。 | zh_TW |
dc.description.abstract | Vasopressin (AVP) is a peptide hormone that regulates water permeability of the kidney collecting ducts. In response to AVP within an hour, AVP mobilizes the water channel protein aquaporin-2 (AQP2) from intracellular storage vesicles to the apical membrane thereby increasing its water permeability. In response to AVP between hours and days, AVP increases overall AQP2 gene expression thereby contributing to water permeability regulation. These two mechanisms are seemingly unrelated. Here, we are proposing a hypothesis that could potentially relate these two processes via α-actinin 4. α-actinin 4 was previously identified in the collecting duct cell model (mpkCCD) in response to AVP stimulation. In one hand, α-actinin 4 being an actin-binding protein could participate in actin cytoskeleton dynamics, a process required for AQP2 trafficking. On the other hand, α-actinin 4 also acts as a transcriptional co-activator of a number of transcription factors including glucocorticoid receptor (GR) that has been implicated in AVP-induced AQP2 gene expression in the mpkCCD cells. It is plausible that AVP may induce α-actinin 4 interaction with GR to trigger AQP2 gene expression. In support of our hypothesis, we found that short hairpin RNA (shRNA)-mediated α-actinin 4 knockdown in the mpkCCD cells reduced AVP-induced AQP2 mRNA and protein levels. α-actinin 4 did not affect AVP-induced AQP2 mRNA stability but partially enhanced AVP-induced AQP2 transcription by activating AQP2 promoter. To investigate the molecule mechanism involved, we found that AVP induced α-actinin 4 nuclear translocation and also increased the amount of GR in the nuclei of the mpkCCD cells. GR knockdown in the mpkCCD cells showed decreased AVP-induced AQP2 mRNA and protein levels. We next found that GR enhanced AVP-induced AQP2 promoter activity by promoter-reporter assay. Above results suggest that GR plays a role in AVP-induced AQP2 expression. Another interesting finding was that GR also appears to regulate vasopressin V2 receptor mRNA levels. In summary, we conclude that α-actinin 4 acts as transcriptional co-activator of GR and regulates AVP-induced AQP2 transcription in the kidney collecting duct cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T06:40:37Z (GMT). No. of bitstreams: 1 ntu-107-R05442017-1.pdf: 1724939 bytes, checksum: a1da7bcf0e154f898c21269f5a5ef0df (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 中文摘要 i
Abstract ii Contents iv Introduction 1 Materials and Methods 4 Results 13 α-actinin 4 knockdown reduced AVP-induced AQP2 mRNA and protein levels in the mpkCCD cells 13 α-actinin 4 did not affect Aqp2 mRNA stability 14 α-actinin 4 partially enhanced AVP-induced Aqp2 transcription by activating AQP2 promoter 14 α-actinin 4 translocated into the nucleus in response to vasopressin 15 Vasopressin increased the amount of glucocorticoid receptor in the nucleus 16 Glucocorticoid receptor knockdown reduced AVP-induced AQP2 mRNA and protein levels in the mpkCCD cells 16 Glucocorticoid receptor enhanced AVP-induced AQP2 promoter activity 18 Glucocorticoid receptor knockdown reduced vasopressin V2 receptor mRNA levels 19 Discussion 20 Figures and Legends 24 Figure 1: α-actinin 4 knockdown reduced AVP-induced AQP2 mRNA and protein levels. 24 Figure 2: α-actinin 4 did not affect Aqp2 mRNA stability. 26 Figure 3: α-actinin 4 partially enhanced AVP-induced Aqp2 gene expression by enhancing AQP2 promoter in the mpkCCD cells. 27 Figure 4: Vasopressin increased the amounts of α-actinin 4 and glucocorticoid receptor in the nuclei of the mpkCCD cells. 28 Figure 5: Glucocorticoid receptor knockdown reduced AVP-induced AQP2 mRNA and protein levels. 29 Figure 6: GR enhanced AVP-induced AQP2 promoter activity in the mpkCCD cells. 31 Figure 7: Vasopressin V2 receptor mRNA levels reduced in the GR knockdown cells. 32 References 34 | |
dc.language.iso | en | |
dc.title | α-輔肌動蛋白4在腎臟集尿管細胞受抗利尿激素誘導第二型水通道蛋白之角色 | zh_TW |
dc.title | Roles of α-actinin 4 in Vasopressin-Induced Aquaporin-2 Expression in the Kidney Collecting Duct Cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 呂紹俊(Shao-Chun Lu),姜至剛(Chih-Kang Chiang) | |
dc.subject.keyword | 抗利尿激素,第二型水通道蛋白,α-輔肌動蛋白4,糖皮質激素受體, | zh_TW |
dc.subject.keyword | Vasopressin,Aquaporin-2,α-actinin 4,glucocorticoid receptor, | en |
dc.relation.page | 36 | |
dc.identifier.doi | 10.6342/NTU201803510 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-08-16 | |
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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