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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余家利(Chia-Li Yu) | |
| dc.contributor.author | Syue-Cian Shiao | en |
| dc.contributor.author | 蕭學謙 | zh_TW |
| dc.date.accessioned | 2021-05-20T20:51:39Z | - |
| dc.date.available | 2012-10-05 | |
| dc.date.available | 2021-05-20T20:51:39Z | - |
| dc.date.copyright | 2011-10-05 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-08 | |
| dc.identifier.citation | 1 Bachmann, S., Metzger, R. & Bunnemann, B. Tamm-Horsfall protein-mRNA synthesis is localized to the thick ascending limb of Henle's loop in rat kidney. Histochemistry 94, 517-523 (1990).
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Am J Kidney Dis 44, 987-999 (2004). 8 Tinschert, S. et al. Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy. Nephrol Dial Transplant 19, 3150-3154, doi:10.1093/ndt/gfh524 (2004). 9 Bleyer, A. J. & Hart, T. C. Familial juvenile hyperuricaemic nephropathy. Qjm 96, 867-868 (2003). 10 Santambrogio, S. et al. Urinary uromodulin carries an intact ZP domain generated by a conserved C-terminal proteolytic cleavage. Biochem Biophys Res Commun 370, 410-413, doi:10.1016/j.bbrc.2008.03.099 (2008). 11 Fletcher, A. P., Neuberger, A. & Ratcliffe, W. A. Tamm-Horsfall urinary glycoprotein. The subunit structure. Biochem J 120, 425-432 (1970). 12 Afonso, A. M. & Marshall, R. D. Observations on the structure of the carbohydrate moieties of the Tamm-Horsfall glycoprotein [proceedings]. Biochem Soc Trans 7, 170-173 (1979). 13 van Rooijen, J. J., Voskamp, A. F., Kamerling, J. P. & Vliegenthart, J. F. Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein. Glycobiology 9, 21-30 (1999). 14 Firon, N., Ofek, I. & Sharon, N. Carbohydrate-binding sites of the mannose-specific fimbrial lectins of enterobacteria. Infect Immun 43, 1088-1090 (1984). 15 Easton, R. L., Patankar, M. S., Clark, G. F., Morris, H. R. & Dell, A. Pregnancy-associated changes in the glycosylation of tamm-horsfall glycoprotein. Expression of sialyl Lewis(x) sequences on core 2 type O-glycans derived from uromodulin. J Biol Chem 275, 21928-21938, doi:10.1074/jbc.M001534200 (2000). 16 Muchmore, A. V. & Decker, J. M. Evidence that recombinant IL 1 alpha exhibits lectin-like specificity and binds to homogeneous uromodulin via N-linked oligosaccharides. J Immunol 138, 2541-2546 (1987). 17 Sherblom, A. P., Decker, J. M. & Muchmore, A. V. The lectin-like interaction between recombinant tumor necrosis factor and uromodulin. J Biol Chem 263, 5418-5424 (1988). 18 Rhodes, D. C., Hinsman, E. J. & Rhodes, J. A. Tamm-Horsfall glycoprotein binds IgG with high affinity. Kidney Int 44, 1014-1021 (1993). 19 Ying, W. Z. & Sanders, P. W. Mapping the binding domain of immunoglobulin light chains for Tamm-Horsfall protein. Am J Pathol 158, 1859-1866, doi:10.1016/S0002-9440(10)64142-9 (2001). 20 Thomas, D. B., Davies, M., Peters, J. R. & Williams, J. D. Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils. Kidney Int 44, 423-429 (1993). 21 Wimmer, T., Cohen, G., Saemann, M. D. & Horl, W. H. Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function. Nephrol Dial Transplant 19, 2192-2197, doi:10.1093/ndt/gfh206 (2004). 22 Yu, C. L. et al. Tamm-Horsfall glycoprotein (THG) purified from normal human pregnancy urine increases phagocytosis, complement receptor expressions and arachidonic acid metabolism of polymorphonuclear neutrophils. Immunopharmacology 24, 181-190 (1992). 23 Saemann, M. D. et al. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism. J Clin Invest 115, 468-475, doi:10.1172/JCI22720 (2005). 24 McGiven, A. R., Hunt, J. S., Day, W. A. & Bailey, R. R. Tamm-Horsfall protein in the glomerular capsular space. J Clin Pathol 31, 620-625 (1978). 25 Rhodes, D. C. Binding of Tamm-Horsfall protein to complement 1q and complement 1, including influence of hydrogen-ion concentration. Immunol Cell Biol 80, 558-566, doi:10.1046/j.1440-1711.2002.01125.x (2002). 26 Saxne, T., Palladino, M. A., Jr., Heinegard, D., Talal, N. & Wollheim, F. A. Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 31, 1041-1045 (1988). 27 Lange, U., Teichmann, J. & Stracke, H. Correlation between plasma TNF-alpha, IGF-1, biochemical markers of bone metabolism, markers of inflammation/disease activity, and clinical manifestations in ankylosing spondylitis. Eur J Med Res 5, 507-511 (2000). 28 Lorenz, H. M. TNF inhibitors in the treatment of arthritis. Curr Opin Investig Drugs 1, 188-193 (2000). 29 Stevenson, F. K. & Kent, P. W. Subunits of Tamm-Horsfall glycoprotein. Biochem J 116, 791-796 (1970). 30 Aderem, A. & Underhill, D. M. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17, 593-623, doi:10.1146/annurev.immunol.17.1.593 (1999). 31 Carroll, M. C. The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 16, 545-568, doi:10.1146/annurev.immunol.16.1.545 (1998). 32 Daeron, M. Fc receptor biology. Annu Rev Immunol 15, 203-234, doi:10.1146/annurev.immunol.15.1.203 (1997). 33 Chimini, G. & Chavrier, P. Function of Rho family proteins in actin dynamics during phagocytosis and engulfment. Nat Cell Biol 2, E191-196, doi:10.1038/35036454 (2000). 34 Lewkowicz, P., Tchorzewski, H., Dytnerska, K., Banasik, M. & Lewkowicz, N. Epidermal growth factor enhances TNF-alpha-induced priming of human neutrophils. Immunol Lett 96, 203-210, doi:10.1016/j.imlet.2004.08.012 (2005). 35 Li, S., Wang, Q., Wang, Y., Chen, X. & Wang, Z. PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration. Mol Endocrinol 23, 901-913, doi:10.1210/me.2008-0368 (2009). 36 Bocker, U. et al. Responsiveness of intestinal epithelial cell lines to lipopolysaccharide is correlated with Toll-like receptor 4 but not Toll-like receptor 2 or CD14 expression. Int J Colorectal Dis 18, 25-32, doi:10.1007/s00384-002-0415-6 (2003). 37 Jiang, Y. et al. Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta). J Biol Chem 271, 17920-17926 (1996). 38 Lechner, C., Zahalka, M. A., Giot, J. F., Moller, N. P. & Ullrich, A. ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation. Proc Natl Acad Sci U S A 93, 4355-4359 (1996). 39 Mertens, S., Craxton, M. & Goedert, M. SAP kinase-3, a new member of the family of mammalian stress-activated protein kinases. FEBS Lett 383, 273-276 (1996). 40 Gum, R. J. et al. Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket. J Biol Chem 273, 15605-15610 (1998). 41 Kuma, Y. et al. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem 280, 19472-19479, doi:10.1074/jbc.M414221200 (2005). 42 Cuenda, A., Cohen, P., Buee-Scherrer, V. & Goedert, M. Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). Embo J 16, 295-305, doi:10.1093/emboj/16.2.295 (1997). 43 Sabio, G. et al. p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. Embo J 24, 1134-1145, doi:10.1038/sj.emboj.7600578 (2005). 44 Cui, J. et al. p38 MAPK contributes to CD54 expression and the enhancement of phagocytic activity during macrophage development. Cell Immunol 256, 6-11, doi:10.1016/j.cellimm.2008.12.003 (2009). 45 Schmidt, M. H. et al. Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal. Nat Cell Biol 11, 873-880, doi:10.1038/ncb1896 (2009). 46 Kansas, G. S. et al. A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion. J Cell Biol 124, 609-618 (1994). 47 Beemiller, P. et al. A Cdc42 activation cycle coordinated by PI 3-kinase during Fc receptor-mediated phagocytosis. Mol Biol Cell 21, 470-480, doi:10.1091/mbc.E08-05-0494 (2010). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9954 | - |
| dc.description.abstract | Tamm-Horsfall glycoprotein (THP) 是由亨利式管(Henle’s loop)中的上行端及遠曲小管所分泌的醣蛋白，分子量約有80-90 KD，其醣分子佔全部重量25-35%，大部分由sialic acid組成。THP 被認具有保護泌尿道表皮細胞免於被病原菌入侵的功能。在先前的研究指出，THP 可以和不同的蛋白質結合: 包括免疫球蛋白輕鏈、第一介白素(IL-1), 補體(complement component) 1q,以及腫瘤壞死因子-α(TNF-α)；然而對於THP如何影響免疫系統其詳細的機制至今依然不清楚，因此我們將THP以各種不同的酵素處理，試圖去了解究竟是THP分子外圍的醣側鏈或是其核心蛋白質結構才具有關鍵性的功能；我們發現THP經不同醣分解酵素處理之後依然具可以刺激多核型白血球的活性，但是THP經蛋白分解酵素處理之後便會失去其功能，所以我們認為THP的核心蛋白結構之重要性是大於側鏈的醣分子。接下來我們發現多核型白血球在p38 的抑制劑(SB 203580)處之後便會失去其吞噬能力，這表示THP和脂多糖(lipopolysaccharide)對於多核型白血球吞噬能力的刺激都是需要p38路徑參與其中。最後我們進一步發現，THP 具有類似表皮生長因子(EGF)刺激多核型白血球的功能，THP 和表皮生長因子都會活化多核型白血球吞噬能力、導致細胞骨架的變化以及ERK1/2的表現；然而一旦我們利用表皮生長因子受體的抑制劑(GW2974)便可以抑制THP和表皮生長因子對多核型白血球的活化能力，但卻不會影響脂多糖對多核型白血球的活化。總結,在論文中我們證明了THP會活化多核型白血球，推測可能藉由THP中EGF-like domain來活化p38以及ERK1/2的訊息傳遞路徑來達成。 | zh_TW |
| dc.description.abstract | Tamm-Horsfall glycoprotein (THP) or uromodulin is produced by renal tubular cells of the ascending limp of Henle’s loop. Tamm-Horsfall glycoprotein is a 80-90KDa GPI-anchored protein and contains approximately 25-35% of carbohydrate-side chain in weight with abundant sialic acid. THP is an important defense molecule in protecting urinary tract epithelial cells from microbial invasion. Our previous data has shown that THP can bind to diverse proteins including immunoglobulin light chains, complement component 1q, interleukin-1(IL-1), and tumor necrosis factor-α (TNF-α).In addition, we found that THP could enhance PMN phagocytosis. However, the mechanism phagocytosis-enhancing activity of THP remained unclear. For further elucidating the mechanism for this activity by THP, we purified THP from normal human urine.
At first, THP was cleaved by different carbohydrate-and protein-degrading enzymes and the data demonstrated that the protein-core structure was more important for activating PMN phagocytosis than carbohydrate-side chains. Next, we found that THP could bind to the surface membrane of PMN and induced phosphorylation of MAP kinase (p38),ERK1/2 and NF-кB signaling pathways. Furthermore, p38 inhibitor SB203580 could abolish LPS and THP induced-PMN phagocytosis. Finally, we found THP and EGF (Epidermal growth factor) exhibited a similar function on PMN and HL-60(human promyelocytic leukemia cells). Our results demonstrated that EGF and THP could induce PMN phagocytosis via rearrangement of cytoskeletal molecules by increasing expression of cdc42, RhoA and Rac. GW2974 (EGFR inhibitor) could reduce the THP- and EGF-induced PMN phagocytosis and ERK1/2 expression in HL-60. In contrast, GW2974 had no effect on LPS-induced PMN phagocytosis. Putting these results together, we concluded that THP used EGF-like domain to stimulate PMN via EGF singling pathway to phosphorylated p38 and ERK1/2. The EGF-like domain in THP molecule may play an important role in PMN phagocytosis-enhancing activity. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T20:51:39Z (GMT). No. of bitstreams: 1 ntu-100-R98448008-1.pdf: 12310364 bytes, checksum: 6d8f84d9cb70bf16acdd61af09e81478 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………… i
中文摘要…………………………………………… ii-iii 英文摘要…………………………………………… iv-v Chapter 1: Introduction…………………………. 2 Chapter 2: Materials and methods……………… 4 Chapter 3: Results………………………………… 11 Chapter4: Discussion……………………………… 17 Chapter5: Conclusion……………………………… 20 Chapter6: Figures…………………………………… 21 Chapter7:References………………………………… 41 | |
| dc.language.iso | en | |
| dc.title | 由尿液純化而來的Tamm-Horsfall glycoprotein 活化中性白血球的分子機制研究 | zh_TW |
| dc.title | Study on the molecular basis of urinary Tamm-Horsfall glycoprotein-induced neutrophils activation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李芳仁(Fang-Jen Lee),蔡長祐(Chang-Youh Tsai) | |
| dc.subject.keyword | Tamm-Horsfall glycoprotein,P38 mitogen-activated protein kinases,多核型白血球吞噬作用,細胞骨架的重組,ERK1/2,EGF樣結構, | zh_TW |
| dc.subject.keyword | Tamm-Horsfall glycoprotein,PMN phagocytosis,P38 mitogen-activated protein kinases,cytoskeleton rearrangement,ERK1/2,EGF-like domain, | en |
| dc.relation.page | 48 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2011-08-08 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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