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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余明俊 | zh_TW |
| dc.contributor.advisor | Ming-Jiun Yu | en |
| dc.contributor.author | 黃晨瑄 | zh_TW |
| dc.contributor.author | Chen-Shiuan Huang | en |
| dc.date.accessioned | 2025-10-07T16:07:59Z | - |
| dc.date.available | 2026-01-01 | - |
| dc.date.copyright | 2025-10-07 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-07-25 | - |
| dc.identifier.citation | Chang, B., K.K.H. Svoboda, and X. Liu, Cell polarization: From epithelial cells to odontoblasts. Eur J Cell Biol, 2019. 98(1): p. 1-11.
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Kortenoeven, M.L., et al., In mpkCCD cells, long-term regulation of aquaporin-2 by vasopressin occurs independent of protein kinase A and CREB but may involve Epac. Am J Physiol Renal Physiol, 2012. 302(11): p. F1395-401. 62. Murillo-de-Ozores, A.R., et al., CREB-family transcription factors and vasopressin-mediated regulation of Aqp2 gene transcription. bioRxiv, 2025. 63. Lin, S.T., et al., Transcription Factor Elf3 Modulates Vasopressin-Induced Aquaporin-2 Gene Expression in Kidney Collecting Duct Cells. Front Physiol, 2019. 10: p. 1308. 64. Field, J. and E. Manser, The PAKs come of age: Celebrating 18 years of discovery. Cell Logist, 2012. 2(2): p. 54-58. 65. Chen, X.-P., et al., PAK2 as a therapeutic target in cancer: Mechanisms, challenges, and future perspectives. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2025. 1880(1): p. 189246. 66. Carmosino, M., et al., Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct. American Journal of Physiology-Renal Physiology, 2007. 292(1): p. F351-F360. 67. Giesecke, T., et al., Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells. J Am Soc Nephrol, 2019. 30(6): p. 946-961. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/100571 | - |
| dc.description.abstract | 腎臟上皮細胞的極性對於進行方向性的物質運輸至關重要，而這個過程仰賴正確的細胞接合結構與動態穩定的肌動蛋白骨架。Pak2是一種 p21活化型激酶，已知在多種細胞中參與細胞骨架與極性的調控，但其在腎臟集尿管細胞中的功能尚未明確。本研究顯示，在腎臟集尿管細胞mpkCCD中降低Pak2表現會使跨上皮電阻下降以及接合蛋白 ZO-1 和 E-cadherin 的錯誤定位，代表細胞極化受損。此外，我們觀察到降低Pak2表現會使細胞質中單體肌動蛋白（G-actin）顯著升高，顯示肌動蛋白聚合受阻。更重要的是，Pak2表現下降也導致腦下垂體加壓素第二型受體（Avpr2）和水通道蛋白2（Aqp2）基因的 mRNA表現量降低，而這兩者皆是血管加壓素（vasopressin）訊號傳導的重要組成。使用細胞骨架聚合抑制劑 cytochalasin D處理細胞，模擬細胞Pak2降低的狀況，同樣可以觀察到提升G-actin水平、破壞細胞極性並抑制Avpr2和Aqp2基因表現，進一步證實G-actin升高對這些效應具有關鍵影響。整體而言，本研究發現 Pak2在維持腎臟集尿管細胞的細胞骨架動態、細胞極性，以及血管加壓素相關基因表達中扮演關鍵角色，並揭示了細胞骨架與基因轉錄之間新的調控連結。 | zh_TW |
| dc.description.abstract | Cell polarization is essential for vectorial transport in renal epithelial cells and relies on proper junctional organization and actin cytoskeletal dynamics. Pak2, a p21-activated kinase, is known to regulate cytoskeletal organization and polarity in various cell types, but its role in kidney collecting duct cells remains unclear. In this study, we show that Pak2 knockdown in kidney collecting duct cells (mpkCCD) disrupts epithelial polarization, as indicated by reduced transepithelial electrical resistance and mis-localization of junctional proteins ZO-1 and E-cadherin. This effect was accompanied by elevated cytoplasmic G-actin levels, suggesting impaired actin polymerization. Notably, Pak2 knockdown also led to decreased mRNA expression of Avpr2 and Aqp2, key components for the vasopressin response. Treatment with cytochalasin D, an actin polymerization inhibitor that increases G-actin, phenocopied the effects of Pak2 knockdown, indicating that elevated G-actin impairs both polarity and gene transcription. These findings identify Pak2 as a critical regulator of actin dynamics, cell polarity, and vasopressin-responsive gene expression in renal collecting duct cells. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-10-07T16:07:59Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-10-07T16:07:59Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 摘要 i
Abstract ii Contents iii Introduction 1 Materials and methods 4 Results 12 Cell polarization was required for Avpr2 and vasopressin-induced AQP2 expression. 12 Pak2 was successfully knocked down in the mpkCCD cells. 13 Pak2 was required for cell polarization, Avpr2 mRNA expression, and vasopressin responses in the mpkCCD cells. 14 Pak2 knockdown had marginal effects on the levels of junctional proteins. 15 Pak2 knockdown altered cellular distribution of junctional proteins. 16 Pak2 knockdown elevated the amount of G-actin in the mpkCCD cells. 17 Cytochalasin D elevated G-actin level in the mpkCCD cells. 17 Cytochalasin D–induced G-actin elevation reduced TEER and decreased Avpr2 and Aqp2 mRNA in mpkCCD cells. 18 Discussion 21 Figures and Legends 25 Figure 1. Cell polarization was required for Avpr2 and vasopressin-induced AQP2 expression. 25 Figure 2. Pak2 was knocked down in the mpkCCD cells. 27 Figure 3. Pak2 was required for cell polarization and expression of Avpr2 and Aqp2 in mpkCCD cells. 29 Figure 4. Pak2 knockdown had marginal effects on the levels of junctional proteins. 31 Figure 5. Pak2 knockdown altered cellular distribution of junctional proteins. 32 Figure 6. Pak2 knockdown elevated G-actin level in the mpkCCD cells. 33 Figure 7. Cytochalasin D elevated G-actin level in the mpkCCD cells. 35 Figure 8. Cytochalasin D–induced G-actin elevation reduced TEER and decreased Avpr2 and Aqp2 mRNA in mpkCCD cells. 36 Figure 9. Hypothetical model 38 References 40 | - |
| dc.language.iso | en | - |
| dc.subject | 上皮細胞 | zh_TW |
| dc.subject | 極化 | zh_TW |
| dc.subject | 水通道蛋白 | zh_TW |
| dc.subject | 抗利尿激素 | zh_TW |
| dc.subject | Pak2 | en |
| dc.subject | epithelial cell | en |
| dc.subject | cell polarization | en |
| dc.subject | vasioressin | en |
| dc.subject | Aquaporin 2 | en |
| dc.title | Pak2對於上皮細胞極化與功能的角色 | zh_TW |
| dc.title | Roles of Pak2 in Epithelial Cell Polarization and Functions | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 陳秉民;潘思宇 | zh_TW |
| dc.contributor.oralexamcommittee | Ping-Min Chen;Szu-Yu Pan | en |
| dc.subject.keyword | 上皮細胞,極化,水通道蛋白,抗利尿激素, | zh_TW |
| dc.subject.keyword | epithelial cell,cell polarization,Aquaporin 2,Pak2,vasioressin, | en |
| dc.relation.page | 48 | - |
| dc.identifier.doi | 10.6342/NTU202502439 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2025-07-28 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | - |
| dc.date.embargo-lift | 2030-07-24 | - |
| 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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