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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余明俊(Ming-Jiun Yu) | |
| dc.contributor.author | Shih-Han Su | en |
| dc.contributor.author | 蘇詩涵 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:29:02Z | - |
| dc.date.available | 2025-08-20 | |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78917 | - |
| dc.description.abstract | 抗利尿激素 (vasopressin，簡稱AVP) 會藉由調控第二型水通道蛋白 (aquaporin-2，簡稱AQP2) 來促進腎臟集尿管中的水分再吸收，AVP刺激下，會增加集尿管細胞中整體AQP2的表現量，並且觸發AQP2往細胞尖頂膜 (apical membrane) 運送，因而增加集尿管細胞的水分通透性。我們先前的研究發現，糖皮質激素受體 (glucocorticoid receptor，簡稱GR) 的活化劑地塞米松 (dexamethasone) 會增加集尿管細胞mpkCCD中AVP誘導的AQP2基因表現，代表GR在AVP刺激下AQP2基因表現上扮演著重要的角色。然而，GR是如何增加AVP誘導的AQP2基因表現並不清楚，在本篇研究中，我們提供可以支持兩個GR調控AVP刺激下AQP2基因表現機制的證據。首先，AVP刺激下，GR的活化輔助因子-輔肌動蛋白4 (-actinin 4) 會進入細胞核內，並協助GR增加AQP2的啟動子活性。第二，GR會維持參與「抗利尿激素調控之水分再吸收」路徑中基因的表現，並抑制參與「雌激素 (estrogen) 訊息傳遞路徑」、「腫瘤壞死因子 (tumor necrosis factor, 簡稱TNF) 訊息傳遞路徑」和「乙型轉化因子 (transforming growth factor-beta, 簡稱TGF-) 訊息傳遞路徑」之基因的表現，這些訊息路徑已知會抑制AQP2基因表現。綜合以上結果，在mpkCCD細胞中，GR會藉由-actinin 4的協助而加強AVP誘導的AQP2基因表現，並維持參與AVP反應和AQP2基因表現之基因的表現。 | zh_TW |
| dc.description.abstract | Vasopressin (AVP) is an antidiuretic hormone that induces water reabsorption by regulating a water channel protein, aquaporin-2 (AQP2), in the kidney collecting ducts. AVP increases overall AQP2 gene expression and triggers AQP2 apical trafficking, thereby increasing water permeability in the collecting duct cells. Our previous study showed that dexamethasone, a glucocorticoid receptor (GR) agonist, enhanced AVP-induced AQP2 gene expression in the collecting duct mpkCCD cells, indicative of a role of GR in AVP-induced AQP2 gene expression. However, how GR mediates AVP-induced AQP2 gene expression was unknown. Here, we provide evidence supporting two mechanisms of GR-mediated AVP-induced AQP2 gene expression. First, in response to AVP, the GR co-activator -actinin 4 translocated into the nucleus and assisted GR to increase AQP2 promoter activity. Second, GR maintained expression of genes involved in “vasopressin-regulated water reabsorption” and repressed expression of genes involved in “estrogen signaling pathway”, “TNF signaling pathway”, and “TGF- signaling pathway” known to suppress AQP2 gene expression. Taken together, these results implicated that GR, assisted by -actinin 4, potentiates AVP-induced AQP2 gene expression and maintains transcriptome profile that permits AVP responses and AQP2 gene expression in the mpkCCD cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:29:02Z (GMT). No. of bitstreams: 1 U0001-1808202015102700.pdf: 3174264 bytes, checksum: 02eecfd1ba7a9bfec96cf1bb0b95828d (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 口試委員審定書 i 中文摘要 ii Abstract iii Contents v Introduction 1 Materials and Methods 7 Results 19 Glucocorticoid receptor knockdown reduced dDAVP-induced AQP2 mRNA level 19 The 1,000bp region upstream to the AQP2 transcription start site was sufficient to mediate GR-enhanced dDAVP-induced promoter activity 20 dDAVP did not induce GR nuclear translocation 21 dDAVP induced ACTN4 nuclear translocation 22 GR knockdown altered transcriptome profile in the mpkCCD cells 23 GR knockdown reduced Avpr2 and Adcy6 mRNA levels 24 Tamoxifen did not increase AQP2 mRNA level in the mpkCCD cells 26 Discussion 28 Figures and Legends 33 Figure 1. Glucocorticoid receptor knockdown reduced dDAVP-induced AQP2 mRNA level. 33 Figure 2. The 1,000bp region upstream to the AQP2 transcription start site was sufficient to mediate GR-enhanced dDAVP-induced promoter activity. 35 Figure 3. dDAVP did not induce GR nuclear translocation. 37 Figure 4. dDAVP induced ACTN4 nuclear translocation. 38 Figure 5. GR knockdown altered transcriptome profile in the mpkCCD cells. 39 Figure 6. GR knockdown reduced Avpr2 and Adcy6 mRNA levels. 40 Figure 7. Three KEGG pathways negatively correlated with AQP2 gene expression. 43 Figure 8. Tamoxifen did not increase AQP2 mRNA level in the mpkCCD cells. 44 Tables 46 Table 1. KEGG pathway analysis of the positive regulators 46 Table 2. KEGG pathway analysis of the negative regulators 49 Table 3. Expression of genes involved in vasopressin-regulated water reabsorption pathway in the control vs. GR knockdown cells based on RNA-seq analysis 51 Table 4. Relative gene expression from RNA-seq and qRT-PCR analysis 54 References 55 | |
| dc.language.iso | zh-TW | |
| dc.subject | 抗利尿激素 | zh_TW |
| dc.subject | a-輔肌動蛋白4 | zh_TW |
| dc.subject | 基因表現 | zh_TW |
| dc.subject | 糖皮質激素受體 | zh_TW |
| dc.subject | 第二型水通道蛋白 | zh_TW |
| dc.subject | gene expression | en |
| dc.subject | aquaporin-2 | en |
| dc.subject | a-actinin 4 | en |
| dc.subject | glucocorticoid receptor | en |
| dc.subject | vasopressin | en |
| dc.title | 糖皮質激素受體在腎臟集尿管細胞中參與並維持抗利尿激素之反應 | zh_TW |
| dc.title | Glucocorticoid Receptor Mediates and Maintains Vasopressin Responses in the Kidney Collecting Duct Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張明富(Ming-Fu Chang),林水龍(Shuie-Liong Lin) | |
| dc.subject.keyword | 抗利尿激素,第二型水通道蛋白,糖皮質激素受體,a-輔肌動蛋白4,基因表現, | zh_TW |
| dc.subject.keyword | vasopressin,aquaporin-2,glucocorticoid receptor,a-actinin 4,gene expression, | en |
| dc.relation.page | 59 | |
| dc.identifier.doi | 10.6342/NTU202003980 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-19 | |
| 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 |
| dc.date.embargo-lift | 2025-08-20 | - |
| 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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