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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余明俊(Ming-Jiun Yu) | |
| dc.contributor.author | Hsiu-Hui Yang | en |
| dc.contributor.author | 楊琇惠 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:07:03Z | - |
| dc.date.available | 2021-12-30 | |
| dc.date.available | 2022-11-24T03:07:03Z | - |
| dc.date.copyright | 2021-12-30 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-12-22 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80458 | - |
| dc.description.abstract | 生物體內所有生理功能的執行均有水分參與，因此維持水分恆定為一個十分重要的課題。在身體處於脫水狀態時，抗利尿激素會釋放至血液中，並和腎臟集尿管細胞上的V2受體結合進而調控第二型水分子通道蛋白(AQP2)以再吸收尿液中的水分。此調控可分為短期調控和長期調控兩類。短期調控可促進細胞頂尖膜下的F-肌動蛋白解聚，使AQP2能運送至頂尖膜上；長期調控則可增加AQP2的基因表達。然而，抗利尿激素是否透過完全分離的機制調節短期和長期調控，或其中有分子連結尚未可知。在本篇論文中，我們證明了alpha-輔肌動蛋白4在細胞內扮演連結短期和長期調控的角色。在抗利尿激素刺激時，alpha-輔肌動蛋白4會離開F-肌動蛋白而進入細胞核，並且在核內扮演糖皮質素受體(為一種基因活化因子)的輔助活化因子，共同增加AQP2的基因表達。在先前的實驗，我們敲低了糖皮質素受體以研究其功能。然而長期敲低糖皮質素受體會造成細胞全轉錄組改變，這些改變亦有可能影響AQP2基因表達。藉由分析信使核糖核酸量變化，我們找出了數個能正向及負向調控AQP2表現的訊息傳遞路徑。從中我們挑出兩個做為研究目標：腫瘤壞死因子訊息傳遞路徑以及轉化生長因子訊息傳遞路徑。在我們的實驗中，加入此二路徑之配體皆可顯著降低AQP2基因表達，顯示了兩者均作為AQP2基因表現之負調控路徑。針對轉化生長因子訊息傳遞路徑我們做了測試。結果顯示轉化生長因子抑制了因抗利尿激素而增加的蛋白激酶B磷酸化，但並不影響AQP2運送至細胞頂尖膜，亦不會造成細胞出現上皮-間質轉化。綜合以上所述，我們的發現指出alpha-輔肌動蛋白4為短期和長期調控間之連結，並且腫瘤壞死因子訊息傳遞路徑以及轉化生長因子訊息傳遞路徑為AQP2基因表現的負調控路徑。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:07:03Z (GMT). No. of bitstreams: 1 U0001-2411202116103500.pdf: 3968622 bytes, checksum: 8643445d4823db83d26693c03245daa9 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | Introduction 1 Materials and Methods 7 Results 16 Vasopressin depolymerized F-actin while freeing a-actinin 4 into cell nucleus 16 Vasopressin enhances interaction between glucocorticoid receptor and a-actinin 4 17 Vasopressin increased nuclear translocation of glucocorticoid receptor in the presence of dexamethasone 17 Glucocorticoid receptor did not bind to putative GR binding sites within 1000 base pairs of the Aqp2 gene promoter 18 Nuclear translocation of glucocorticoid receptor was independent of a-actinin 4 19 Vasopressin-induced GR nuclear translocation is independent of dexamethasone 19 Alpha-actinin 4 knockdown reduced AQP2 mRNA level in the absence of dexamethasone 20 Glucocorticoid receptor knockdown suppressed transcription of genes involved in the TNF signaling pathway 21 Glucocorticoid receptor knockdown suppressed transcription of genes involved in TGFb signaling pathway 22 Inhibitors of TNF and TGFb receptor did not increase AQP2 mRNA in the absence of vasopressin 23 TNFa and TGFb1 ligand reduced Aqp2 gene expression 23 TGFb1 did not influence vasopressin-induced apical AQP2 trafficking 24 TGFb1 did not induce epithelial to mesenchymal transition (EMT) of mpkCCD cells 25 TGFb1 reduced vasopressin-induced Akt phosphorylation in the mpkCCD cells. 26 Discussion 28 Figures and Legends 33 Tables 56 References 59 | |
| dc.language.iso | en | |
| dc.subject | 第二型水通道蛋白 | zh_TW |
| dc.subject | 集尿管 | zh_TW |
| dc.subject | 轉化生長因子 | zh_TW |
| dc.subject | aquaporin 2 | en |
| dc.subject | TGF beta | en |
| dc.subject | collecting duct | en |
| dc.title | 轉化生長因子 beta 1抑制腎臟集尿管細胞中由抗利尿激素促進之第二型水通道蛋白基因表達 | zh_TW |
| dc.title | TGF beta 1 Suppresses Vasopressin-Induced Aquaporin 2 Gene Expression in the Kidney Collecting Duct Cells | en |
| dc.date.schoolyear | 110-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林水龍(Hsin-Tsai Liu),顏伯勳(Chih-Yang Tseng) | |
| dc.subject.keyword | 第二型水通道蛋白,轉化生長因子,集尿管, | zh_TW |
| dc.subject.keyword | aquaporin 2,TGF beta,collecting duct, | en |
| dc.relation.page | 65 | |
| dc.identifier.doi | 10.6342/NTU202104491 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-12-22 | |
| 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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