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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29004完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林思洸 | |
| dc.contributor.author | Chen-En Wu | en |
| dc.contributor.author | 吳承恩 | zh_TW |
| dc.date.accessioned | 2021-06-13T00:34:22Z | - |
| dc.date.available | 2007-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2007-07-25 | |
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Si， W.， et al.， CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells. Mol Cell Biol， 2006. 26（8）: p. 2955-64. 25. Chen， C.C.， F.E. Mo， and L.F. Lau， The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts. J Biol Chem， 2001. 276（50）: p. 47329-37. 26. Han， J.S.， et al.， Regulation of Cyr61/CCN1 gene expression through RhoA GTPase and p38MAPK signaling pathways. Eur J Biochem， 2003. 270（16）: p. 3408-21. 27. Schutze， N.， et al.， 5' flanking sequence of the human immediate early responsive gene ccn1 （Cyr61） and mapping of polymorphic CA repeat sequence motifs in the human ccn1 （Cyr61） locus. Mol Pathol， 2001. 54（3）: p. 170-5. 28. Yang， C.， et al.， A role for CREB binding protein and p300 transcriptional coactivators in Ets-1 transactivation functions. Mol Cell Biol， 1998. 18（4）: p. 2218-29. 29. Magenta， A.， et al.， MyoD stimulates RB promoter activity via the CREB/p300 nuclear transduction pathway. Mol Cell Biol， 2003. 23（8）: p. 2893-906. 30. Negritto， M.C.， et al.， Novel function of Rad27 （FEN-1） in restricting short-sequence recombination. Mol Cell Biol， 2001. 21（7）: p. 2349-58. 31. Shikama， N.， et al.， Functional interaction between nucleosome assembly proteins and p300/CREB-binding protein family coactivators. Mol Cell Biol， 2000. 20（23）: p. 8933-43. 32. Chan， H.M. and N.B. La Thangue， p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci， 2001. 114（Pt 13）: p. 2363-73. 33. Collingwood， T.N.， F.D. Urnov， and A.P. Wolffe， Nuclear receptors: coactivators， corepressors and chromatin remodeling in the control of transcription. J Mol Endocrinol， 1999. 23（3）: p. 255-75. 34. Davie， J.R. and D.N. Chadee， Regulation and regulatory parameters of histone modifications. J Cell Biochem Suppl， 1998. 30-31: p. 203-13. 35. Lin， S.K.， et al.， MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum， 2004. 50（3）: p. 785-93. 36. de Hooge， A.S.， et al.， Adenoviral transfer of murine oncostatin M elicits periosteal bone apposition in knee joints of mice， despite synovial inflammation and up-regulated expression of interleukin-6 and receptor activator of nuclear factor-kappa B ligand. Am J Pathol， 2002. 160（5）: p. 1733-43. 37. Zhu， X.S.， et al.， Transcriptional scaffold: CIITA interacts with NF-Y， RFX， and CREB to cause stereospecific regulation of the class II major histocompatibility complex promoter. Mol Cell Biol， 2000. 20（16）: p. 6051-61. 38. Zika， E. and J.P. Ting， Epigenetic control of MHC-II: interplay between CIITA and histone-modifying enzymes. Curr Opin Immunol， 2005. 17（1）: p. 58-64. 39. Buttice， G.， et al.， Interferon-gamma induces major histocompatibility class II transactivator （CIITA）， which mediates collagen repression and major histocompatibility class II activation by human aortic smooth muscle cells. Circ Res， 2006. 98（4）: p. 472-9. 40. Xu， Y.， et al.， Major histocompatibility class II transactivator （CIITA） mediates repression of collagen （COL1A2） transcription by interferon gamma （IFN-gamma）. J Biol Chem， 2004. 279（40）: p. 41319-32. 41. Zhu， X.S. and J.P. Ting， A 36-amino-acid region of CIITA is an effective inhibitor of CBP: novel mechanism of gamma interferon-mediated suppression of collagen alpha（2）（I） and other promoters. Mol Cell Biol， 2001. 21（20）: p. 7078-88. 42. Sisk， T.J.， et al.， MHC class II transactivator inhibits IL-4 gene transcription by competing with NF-AT to bind the coactivator CREB binding protein （CBP）/p300. J Immunol， 2000. 165（5）: p. 2511-7. 43. LeibundGut-Landmann， S.， et al.， Mini-review: Specificity and expression of CIITA， the master regulator of MHC class II genes. Eur J Immunol， 2004. 34（6）: p. 1513-25. 44. Swanberg， M.， et al.， MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis， multiple sclerosis and myocardial infarction. Nat Genet， 2005. 37（5）: p. 486-94. 45. Cenci， S.， et al.， Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci U S A， 2003. 100（18）: p. 10405-10. 46. Inohara， N. and G. Nunez， NODs: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol， 2003. 3（5）: p. 371-82. 47. Ito， A.， et al.， p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. Embo J， 2001. 20（6）: p. 1331-40. 48. Xu， L.， C.K. Glass， and M.G. Rosenfeld， Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev， 1999. 9（2）: p. 140-7. 49. Jepsen， K. and M.G. Rosenfeld， Biological roles and mechanistic actions of co-repressor complexes. J Cell Sci， 2002. 115（Pt 4）: p. 689-98. 50. Dignam， J.D.， R.M. Lebovitz， and R.G. Roeder， Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res， 1983. 11（5）: p. 1475-89. 51. Li， Q.， H. Xiao， and K. Isobe， Histone acetyltransferase activities of cAMP-regulated enhancer-binding protein and p300 in tissues of fetal， young， and old mice. J Gerontol A Biol Sci Med Sci， 2002. 57（3）: p. B93-8. 52. Steimle， V.， et al.， Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency （or bare lymphocyte syndrome）. Cell， 1993. 75（1）: p. 135-46. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29004 | - |
| dc.description.abstract | 類風濕性關節炎是一種自體免疫細胞攻擊軟骨組織造成關節部分的慢性發炎反應，病人常因骨骼及軟組織受破壞影響關節的正常功能。此病的盛行率約為1％。2006年，Christian S. Haas 利用cDNA microarray分析病人檢體，發現一個血管新生因子cysteine-rich， angiogenic inducer 61，Cyr61 （a known angiogenic factor） 的表現有顯著差異，然而其在疾病的過程扮演著正面或負面的角色仍然不清楚。我們實驗室透過在成骨細胞（U2OS， an osteoblast-like osteosarcoma cell line） 加入有活性的Cyr61合成蛋白以及轉染表現質體Cyr61/pCDNA3.1均發現，這個蛋白質可以促進細胞爬行（migration）的能力。此外，一個能夠促進成骨細胞分化及成熟的蛋白質，抑瘤素 Oncostatin M，OSM （IL-6家族成員之一），我們實驗室也發現它能夠透過一連串細胞內訊號導致磷酸化CREB （cAMP response element-binding）蛋白質促進Cyr61的表現。確認了成骨細胞Cyr61基因的表現模式後，本文旨在研究是否有其他扮演調控的因子參與其中。CIITA （MHC Class II transactivatoir），是表現MHC class II重要的調控因子，但是，在表現其他基因，例如collagen type I，則被認為是一個抑制者。透過西方墨點轉漬法以及promoter activity的分析，我們確認了CIITA在Cyr61表現上扮演著抑制的角色。CIITA沒有DNA binding domain而需要透過其他轉錄因子，例如CREB，NF-Y及RFX等，結合在特定的位置。於是，我們推論透過CREB的幫助，CIITA整併到Cyr61 promoter處。接著，我們把Cyr61 promoter region的CRE site （CREB binding site）進行突變，也的確發現了CIITA抑制mutant Cyr61 promoter activity的能力明顯變弱。對於CIITA弱化Cyr61基因表現可能的機轉，目前我們發現CIITA的存在會抑制CREB的磷酸化，不僅影響CREB與Cyr61 promoter的結合也阻礙了CREB 與p300之間直接的互動。研究成果展現了CIITA在Cyr61基因表現過程當中扮演抑制者可能的機制與角色。也更加清楚OSM所誘導的Cyr61轉錄的作用機制。 | zh_TW |
| dc.description.abstract | AIMS: To evaluate the possible role of human Cyr61 in rheumatoid arthritis and the regulation mechanisms of Cyr61 gene expression by class II transactivator in human osteoblasts.
METHODS AND RESULTS: 1.） We assessed the transcriptional regulation of oncostatin-M （OSM）-induced Cyr61 gene expression in U2OS, a human osteosarcoma cell line with osteoblastic characters. Western blot revealed that OSM induced obvious Cyr61 synthesis and phsphorylation of cAMP responsive binding protein （CREB）. Luciferase assay showed elevated Cyr61 promoter activities following CREB over-expression. Electrophoretic mobility shift assay （EMSA） revealed significant CREB/DNA cross-talk after OSM stimulation. But, Dominant negative p300 showed no significant difference in inducing Cyr61 expression versus vector only in luciferase assay. 2.） We studied the regulation of class transcactivator （CIITA）. Western blot revealed that CIITA expression reduced Cyr61 expression and attenuated CREB activity. Luciferase assay showed CIITA regulates Cyr61 expressionin a dose-dependent manner CIITA and suppression on Cyr61 gene expression is CRE-dependent. CO-IP data indicated that CIITA reduced the binding between CREB / p300. 3.） In RA animal model we saw clearly ankylosis, bone resorption and granulation tissue infiltration. IHC data showed us Cyr61 expression in tissue-specific manner. CONCLUSION: CREB phosphorylation and HAT activity of p300 was critical for Cyr61 gene expression. Class II transactivator suppressed Cyr61 transcription by sequester CREB and result in attenuating CREB / p300 binding. In vivo examination showed that Cyr61 expression in rheumatoid arthritis rat is cell and tissue specific. INPACT OF THIS STUDY: This study provided the regulation mechanisms of Cyr61 gene expression in human osteoblasts and indicated a close relationship between Cyr61 expression and rheumatoid arthritis pathology. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T00:34:22Z (GMT). No. of bitstreams: 1 ntu-95-R94450012-1.pdf: 8139714 bytes, checksum: 6fabaaf3765bdec14dcc551ec6682d2f (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄 i
圖次 iii 謝誌 iv 中文摘要 1 英文摘要 2 1. 第一章 導論 4 1.1. 類風濕性關節炎 4 1.2. Cyr61與類風溼性關節炎 4 1.3. CREB與p300 7 1.4. OSM 8 1.5. Class II transactivator 8 2. 第二章 實驗目的 10 3. 第三章 材料與方法 11 3.1. 實驗細胞株 11 3.2. 實驗質體 11 3.3. EMSA Probe sequence 12 3.4. Purified Protein 12 3.5. Transient transfection 12 3.6. 細胞內蛋白質的萃取 13 3.7. 細胞核內蛋白質的萃取 15 3.8. Immunopresentation 〈IP〉 17 3.9. 西方墨點法 18 3.10. Electrophoretic Mobility Shift Assay〈EMSA〉 19 3.11. Luciferase assay 20 3.12. Histone acetyltransferase activity〈HAT〉assay 22 3.13. 統計方法 22 3.14. Collagen induced arthritis in Rat 22 4. 第四章 實驗結果 24 4.1. OSM透過CREB的磷酸化，刺激造骨細胞 Cyr61的基因表現 24 4.2. Class II transactivator（CIITA）能夠調控造骨細胞Cyr61的表現 25 4.3. 建立類風濕性關節炎之大鼠實驗動物模式 27 5. 第五章 討論 29 5.1. 活化的CREB能夠促使Cyr61基因表現，並且這個過程 需要p300的HAT酵素活性 29 5.2. CIITA 影響Cyr61基因表現之調控機制 31 5.2.1. Collagen-induced arthritis rat 36 6. 第六章 結論 38 參考文獻 60 | |
| dc.language.iso | zh-TW | |
| dc.title | Class II transactivator抑制人類造骨細胞Cyr61基因表現的機制 | zh_TW |
| dc.title | Class II Transactivator Suppresses Human Osteoblastic Cyr61 Gene Expression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 郭彥彬 | |
| dc.contributor.oralexamcommittee | 蕭宏昇 | |
| dc.subject.keyword | 類風溼性關節炎,Cyr61,CIITA,CREB,p300, | zh_TW |
| dc.subject.keyword | Rheumatoid arthritis,Cyr61,CIITA,CREB,p300, | en |
| dc.relation.page | 66 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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