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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李永凌(Yung-Ling Lee) | |
| dc.contributor.author | Ming-Fong Yang | en |
| dc.contributor.author | 楊明方 | zh_TW |
| dc.date.accessioned | 2021-06-15T13:27:05Z | - |
| dc.date.available | 2026-02-16 | |
| dc.date.copyright | 2016-02-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-02-18 | |
| dc.identifier.citation | 1. Parisi, R., et al., Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol, 2013. 133(2): p. 377-85.
2. de Korte, J., et al., Quality of life in patients with psoriasis: a systematic literature review. J Investig Dermatol Symp Proc, 2004. 9(2): p. 140-7. 3. Nestle, F.O., D.H. Kaplan, and J. Barker, Psoriasis. N Engl J Med, 2009. 361(5): p. 496-509. 4. Boehncke, W.H. and M.P. Schon, Psoriasis. Lancet, 2015. 386(9997): p. 983-94. 5. Organization, W.H., World psoriasis day—document EB133.R2, agenda item 6.2, in World Health Assembly. May 30, 2013. 6. Langley, R.G., G.G. Krueger, and C.E. Griffiths, Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis, 2005. 64 Suppl 2: p. ii18-23; discussion ii24-5. 7. Griffiths, C.E. and J.N. Barker, Pathogenesis and clinical features of psoriasis. Lancet, 2007. 370(9583): p. 263-71. 8. Guttman-Yassky, E., K.E. Nograles, and J.G. Krueger, Contrasting pathogenesis of atopic dermatitis and psoriasis--part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol, 2011. 127(6): p. 1420-32. 9. Siemes, C., et al., Normalized proliferation of normal and psoriatic keratinocytes by suppression of sAPPalpha-release. J Invest Dermatol, 2004. 123(3): p. 556-63. 10. Lauc, G., J. Kristic, and V. Zoldos, Glycans - the third revolution in evolution. Front Genet, 2014. 5: p. 145. 11. Schedin-Weiss, S., B. Winblad, and L.O. Tjernberg, The role of protein glycosylation in Alzheimer disease. FEBS J, 2014. 281(1): p. 46-62. 12. Goulabchand, R., et al., Impact of autoantibody glycosylation in autoimmune diseases. Autoimmun Rev, 2014. 13(7): p. 742-50. 13. Savinova, O.V., et al., Reduced apolipoprotein glycosylation in patients with the metabolic syndrome. PLoS One, 2014. 9(8): p. e104833. 14. Pinho, S.S. and C.A. Reis, Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer, 2015. 15(9): p. 540-55. 15. Moremen, K.W., M. Tiemeyer, and A.V. Nairn, Vertebrate protein glycosylation: diversity, synthesis and function. Nat Rev Mol Cell Biol, 2012. 13(7): p. 448-62. 16. Tu, Z., Y.N. Lin, and C.H. Lin, Development of fucosyltransferase and fucosidase inhibitors. Chem Soc Rev, 2013. 42(10): p. 4459-75. 17. Nakayama, F., et al., Expression of cutaneous lymphocyte-associated antigen regulated by a set of glycosyltransferases in human T cells: involvement of alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I. J Invest Dermatol, 2000. 115(2): p. 299-306. 18. Mizukawa, Y., et al., Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin lesions of atopic dermatitis patients. Exp Dermatol, 2008. 17(3): p. 170-6. 19. Renkonen, J., et al., Glycosylation might provide endothelial zip codes for organ-specific leukocyte traffic into inflammatory sites. Am J Pathol, 2002. 161(2): p. 543-50. 20. Information, T.N.C.f.B. Gene Expression Omnibus. 21. Bigler, J., et al., Cross-study homogeneity of psoriasis gene expression in skin across a large expression range. PLoS One, 2013. 8(1): p. e52242. 22. Suarez-Farinas, M., et al., Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis. J Invest Dermatol, 2012. 132(11): p. 2552-64. 23. Reischl, J., et al., Increased expression of Wnt5a in psoriatic plaques. J Invest Dermatol, 2007. 127(1): p. 163-9. 24. Swindell, W.R., et al., Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis. PLoS One, 2012. 7(3): p. e34594. 25. Kulski, J.K., et al., Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals. J Mol Med (Berl), 2005. 83(12): p. 964-75. 26. Chen, C.Y., et al., Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer. Proc Natl Acad Sci U S A, 2013. 110(2): p. 630-5. 27. Cheng, L., et al., FUT family mediates the multidrug resistance of human hepatocellular carcinoma via the PI3K/Akt signaling pathway. Cell Death Dis, 2013. 4: p. e923. 28. Ito, Y., et al., Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer Lett, 2003. 200(2): p. 167-72. 29. Wang, X., et al., Overexpression of alpha (1,6) fucosyltransferase associated with aggressive prostate cancer. Glycobiology, 2014. 24(10): p. 935-44. 30. Fleischer, A.B., Jr., et al., Patient measurement of psoriasis disease severity with a structured instrument. J Invest Dermatol, 1994. 102(6): p. 967-9. 31. Oriol Arqués, I.C., Stephan Tenbaum, Isabel Puig & Héctor G. Palmer, Standardized Relative Quantification of Immunofluorescence Tissue Staining. Protocol Exchange, 2012. 2. 32. Chen, H.L., et al., Galectin-7 Regulates Keratinocyte Proliferation and Differentiation through JNK-miR-203-p63 Signaling. J Invest Dermatol, 2015. 33. Pena-Diaz, J., et al., Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication. Nucleic Acids Res, 2013. 41(5): p. 2846-56. 34. He, Y.Y., J.L. Huang, and C.F. Chignell, Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization. Oncogene, 2006. 25(10): p. 1521-31. 35. Madonna, S., et al., Anti-apoptotic effects of suppressor of cytokine signaling 3 and 1 in psoriasis. Cell Death Dis, 2012. 3: p. e334. 36. Alam, H., et al., Novel function of keratins 5 and 14 in proliferation and differentiation of stratified epithelial cells. Mol Biol Cell, 2011. 22(21): p. 4068-78. 37. Man, X.Y., et al., Analysis of epithelial-mesenchymal transition markers in psoriatic epidermal keratinocytes. Open Biol, 2015. 5(8). 38. Yamane-Ohnuki, N. and M. Satoh, Production of therapeutic antibodies with controlled fucosylation. MAbs, 2009. 1(3): p. 230-6. 39. Mrowietz, U., et al., Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res, 2011. 303(1): p. 1-10. 40. Heenen, M. and T. Simonart, Apoptosis in psoriatic epidermis. J Cutan Pathol, 2008. 35(3): p. 346. 41. Wrone-Smith, T., et al., Keratinocytes derived from psoriatic plaques are resistant to apoptosis compared with normal skin. Am J Pathol, 1997. 151(5): p. 1321-9. 42. Mendoza, M.C., E.E. Er, and J. Blenis, The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci, 2011. 36(6): p. 320-8. 43. Alam, S., et al., EGFR-mediated Akt and MAPKs signal pathways play a crucial role in patulin-induced cell proliferation in primary murine keratinocytes via modulation of Cyclin D1 and COX-2 expression. Mol Carcinog, 2014. 53(12): p. 988-98. 44. Masuda, M., et al., Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res, 2002. 62(12): p. 3351-5. 45. Brand, T.M., et al., The nuclear epidermal growth factor receptor signaling network and its role in cancer. Discov Med, 2011. 12(66): p. 419-32. 46. Wang, Y., et al., Loss of alpha1,6-fucosyltransferase suppressed liver regeneration: implication of core fucose in the regulation of growth factor receptor-mediated cellular signaling. Sci Rep, 2015. 5: p. 8264. 47. Gu, W., et al., alpha1,6-Fucosylation regulates neurite formation via the activin/phospho-Smad2 pathway in PC12 cells: the implicated dual effects of Fut8 for TGF-beta/activin-mediated signaling. FASEB J, 2013. 27(10): p. 3947-58. 48. Wang, X., et al., Requirement of Fut8 for the expression of vascular endothelial growth factor receptor-2: a new mechanism for the emphysema-like changes observed in Fut8-deficient mice. J Biochem, 2009. 145(5): p. 643-51. 49. Liu, Y.C., et al., Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc Natl Acad Sci U S A, 2011. 108(28): p. 11332-7. 50. Man, X.Y., et al., Overexpression of vascular endothelial growth factor (VEGF) receptors on keratinocytes in psoriasis: regulated by calcium independent of VEGF. J Cell Mol Med, 2008. 12(2): p. 649-60. 51. Nanney, L.B., et al., Altered [125I]epidermal growth factor binding and receptor distribution in psoriasis. J Invest Dermatol, 1986. 86(3): p. 260-5. 52. Hinz, J.M., T. Helleday, and M. Meuth, Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3. Carcinogenesis, 2003. 24(2): p. 249-53. 53. van Horssen, R., T.L. Ten Hagen, and A.M. Eggermont, TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist, 2006. 11(4): p. 397-408. 54. Bekisz, J., et al., Antiproliferative Properties of Type I and Type II Interferon. Pharmaceuticals (Basel), 2010. 3(4): p. 994-1015. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51190 | - |
| dc.description.abstract | 背景：
乾癬是一個常見、遺傳性的慢性發炎皮膚疾病，其重要特徵為表皮角質細胞異常增生及分化，而導致表皮增厚。第八型岩藻醣轉移酶(α1,6-fucosyltransferase , Fut8)，是一個將岩藻醣基從GDP轉移到核心醣胜肽N-linked acetylglucosamine (GlcNAc)的酵素，此反應被稱作核心岩藻醣化(core fucosylation)。許多研究已證實，核心岩藻醣化參與許多病理生理過程，例如在癌細胞轉移及細胞不正常增生扮演很重要的角色。本研究探討Fut8在角質細胞的表達與乾癬嚴重程度的相關性，並證明Fut8會促進皮膚角質細胞的增生。 方法： 做法上，我們從Taiwanese Skin Inflammatory Disease Consortium收集乾癬病患的皮膚檢體整合成生物樣本庫，比較皮膚組織切片中Fut8的表達量與乾癬疾病嚴重程度的相關性；本研究同時建立FUT8變異的轉植皮膚角質細胞株，並利用WST-1 assay 以及活細胞長時間影像，探討FUT8的過度表達或基因抑制是否會影響角質細胞增生。最後，以胸苷細胞週期同步化 (double thymidine block cell cycle synchronization)，探討FUT8過度表達與基因抑制如何影響細胞週期，以及細胞週期調控蛋白的表現。 結果： 本研究納入七位乾癬患者，發現在較嚴重的乾癬患者中，Fut8在患部的表現大於非患部。免疫染色顯示Fut8在乾癬患部表皮的表現與角蛋白14 (keratin 14)的表現區域重疊。本研究另在細胞實驗上證實FUT8過度表達會促進角質細胞的增生，而抑制FUT8基因會降低角質細胞的增生；胸苷細胞周期同步化結果顯示，FUT8過度表達會促進角質細胞的細胞週期S期，進而加速細胞分裂，並促進週期蛋白D1、週期蛋白A2以及週期蛋白B1的表現；相反地，抑制FUT8基因會造成G2/M期細胞週期遲滯，並抑制週期蛋白B1的表現。 本研究證實Fut8與乾癬嚴重程度的相關性及Fut8調控角質細胞的增生，Fut8可望為治療乾癬，以及其他角質細胞異常增生的皮膚疾病的分子標靶。 | zh_TW |
| dc.description.abstract | Background:
Psoriasis is a common, heritable, and chronic inflammatory skin disorder. Epidermal thickness is an important index of psoriasis severity and is directly caused by keratinocyte hyperproliferation. Fucosyltransferase 8 (Fut8) is the only enzyme catalyzing α1,6-fucosylation in mammal and has been observed to regulate cell proliferaton in various malignant cancer. This study aimed to investigate the relationship between Fut8 and psoriasis severity as well as further elucidate how Fut8 regulates keratinocyte proliferation. Methods: Our skin tissue bio-bank, Taiwanese Skin Inflammatory Disease Consortium, included skin biopsy samples collected from psoriasis patients. Fut8 expression in skin biopsy was examined with immunohistochemistry and immunofluorescence. The correlations between clinical features of psoriasis patients and Fut8 expression levels in skin biopsy were analyzed. In addition, stable cell clones of FUT8 overexpression or knockdown were established in HaCaT cells, an immortalized human keratinocyte cell line. WST-1 (2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt) cell proliferation assay and time-lapse microscopy were used to investigate whether Fut8 overexpression or knockdown affects keratinocyte proliferation. Double thymidine block was applied to synchronize cell cycle and expression of cell cycle regulators was examined. Results: Among the seven psoriasis patients recruited in this study, FUT8 expression tended to be upregulated in lesional epidermis from patients with more severe psoriasis. Fut8 was upregulated in psoriasis lesional epidermis and colocalized with keratin 14. Overexpressing FUT8 in HaCaT cells promoted cell proliferation, while FUT8 knockdown inhibited HaCaT cell proliferation. Under double-thymidine block cell cycle synchronization, overexpressing FUT8 in HaCaT cells accelerated cell proliferation by promoting G1-to-S phase transition and inducing cyclin A2, cyclin D and cyclin B1 expression. On the contrary, FUT8 knockdown caused cell cycle retardation by G2/M phase arrest through down-regulation of cyclin B1. Our study revealed the potential roles of Fut8 in psoriasis severity and keratinocyte proliferation. We believe that Fut8 may be a promising therapeutic target for psoriasis and possibly other skin inflammation diseases which involve dysregulated keratinocyte proliferation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T13:27:05Z (GMT). No. of bitstreams: 1 ntu-105-R02849005-1.pdf: 1696078 bytes, checksum: b5eeff46b5764ce21045311c8fb3fed0 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | Directory
1. Introduction 1 1.1. Skin inflammation and psoriasis 1 1.2. Fucosyltransferases and skin inflammation 2 1.3. Association of FUT8 and psoriasis in microarray studies 4 1.4. FUT8 and cell proliferation 5 2. Specific Aims 6 3. Material and Methods 7 3.1 Study Subjects 7 3.1.1 Skin biopsy sample collection from psoriasis patients 7 3.2 Immunohistochemistry (IHC) 8 3.3 Immunofluorescence (IF) 8 3.4 Human keratinocyte culture 9 3.5 FUT8 overexpression using cDNA Lentiviral transduction 9 3.6 FUT8 knockdown using shRNA lentiviral transduction 9 3.7 Lens Culinaris Agglutinin (LCA) staining and cell sorting 10 3.8 Cell proliferation assay 10 3.8.1 WST-1 cell proliferation assay 10 3.8.2 Time-lapse Microscope 11 3.8.3 HaCaT cell synchronization 11 3.9 Apopotosis induction and Annexin V assay 12 3.10 Western blotting 12 3.11 Statistical analysis 13 4. Results 15 4.1 Upregulation of FUT8 expression in psoriasis lesional skin 15 4.2 Correlation between FUT8 expression and clinicopathological factors in psoriasis 16 4.3 Changes of cell surface core- fucosylation of FUT8 mutant keratinocyte cell line 17 4.4 FUT8 regulates cell proliferation in HaCaT cells 18 4.5 FUT8 regulates cell proliferation by regulating cell cycle 19 4.6 FUT8 expression and keratinocyte apoptosis 21 5. Discussion 22 5.1 The relationship of FUT8 and psoriasis 22 5.2 Cell surface core-fucosylation and cell proliferation 22 5.3 Possible mechanisms of Fut8 regulating keratinocyte proliferation 23 5.3 FUT8 and keratinocyte apoptosis 25 5.4 Future translational perspective 26 6. References 27 Figures and Tables Figure 1. Comparison of FUT expression between psoriasis lesional and nonlesional skin samples in six microarray datasets 33 Figure 2. IHC and IF staining of FUT8 expression in psoriasis lesional and nonlesional skin 34 Figure 3. Co-staining of FUT8 and Keratin 14 in psoriasis lesional and nonlesional skin 35 Figure 4. FUT8 overexpression and knockdown in HaCaT cells 36 Figure 5. LCA staining core fucosylation on cell surface 37 Figure 6. WST-1 cell proliferation assay 38 Figure 7. Time-lapse microscopy cell proliferation assay 39 Figure 8. Overexpressing FUT8 in HaCaT cells promoted cell proliferation by regulating cell cycle 40 Figure 9. Upregulation of cyclins in FUT8 overexpressed HaCaT cells 41 Figure 10. Knockdown FUT8 in HaCaT cells inhibited cell proliferation by cell cycle retardation 42 Figure 11. Cell cycle profiles of FUT8 knockdown HaCaT cells and control cells 43 Figure 12. Knockdown FUT8 in HaCaT cells inhibited cell proliferation by slowdown cell cycle 44 Figure 13. FUT8 overexpression may not affect HaCaT cell apoptosis. FUT8 knockdown might promote TNF- /IFN- induced apoptosis 45 Table 1. Microarray analysis of FUT8 expression in microarray datasets 46 Table 2. Correlation of epidermal FUT8 expression and clinicopathological factors in seven psoriasis patients 47 | |
| dc.language.iso | en | |
| dc.subject | 第八型岩藻醣轉移? | zh_TW |
| dc.subject | 乾癬 | zh_TW |
| dc.subject | 角質細胞 | zh_TW |
| dc.subject | 細胞週期 | zh_TW |
| dc.subject | 週期蛋白 | zh_TW |
| dc.subject | 乾癬 | zh_TW |
| dc.subject | 角質細胞 | zh_TW |
| dc.subject | 第八型岩藻醣轉移? | zh_TW |
| dc.subject | 細胞週期 | zh_TW |
| dc.subject | 週期蛋白 | zh_TW |
| dc.subject | keratinocytes | en |
| dc.subject | keratinocytes | en |
| dc.subject | fucosyltransferase 8 | en |
| dc.subject | cell cycle | en |
| dc.subject | cyclin | en |
| dc.subject | Psoriasis | en |
| dc.subject | cyclin | en |
| dc.subject | cell cycle | en |
| dc.subject | fucosyltransferase 8 | en |
| dc.subject | Psoriasis | en |
| dc.title | 探討第八型岩藻醣轉移酶在乾癬角質細胞增生的角色 | zh_TW |
| dc.title | Role of Fucosyltransferase 8 Regulating Keratinocyte Proliferation in Psoriasis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 嚴仲陽(Jong-Young Yen),金傳春(Chwan-Chuen King),安形高志(Takashi Angata) | |
| dc.subject.keyword | 乾癬,角質細胞,第八型岩藻醣轉移?,細胞週期,週期蛋白, | zh_TW |
| dc.subject.keyword | Psoriasis,keratinocytes,fucosyltransferase 8,cell cycle,cyclin, | en |
| dc.relation.page | 47 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-02-18 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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