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人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分...

林育賢

人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分子機制研究= Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts/

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分子機制研究= / 林育賢
其他題名:	Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts/
其他題名:	Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts
作者:	林育賢
出版者:	[高雄市]: [撰者], : 民111,
面頁冊數:	77葉: 圖; : 30公分;
附註:	指導教授: 陳瑩容.
提要註:	慢性傷口中的發炎因子TNF-α調控金屬蛋白酶組織抑制劑(TIMPs) 活性，延遲傷口癒合過程。TNF-α活化轉錄因子NF-κB調控目標基因表達外，TNF-α也被報導調控EZH2組蛋白甲基轉移酶表現，但尚未有研究釐清在皮膚細胞中TNF-α對EZH2和TIMPs的調控機轉。研究中TNF-α誘導EZH2和TIMP-2 mRNA和蛋白質表現上升。探討TNF-α是否透過EZH2下調TIMP-2表現，細胞處理EZH2甲基轉移酶抑制劑(GSK126)，當EZH2活性受抑制會回復TNF-α對TIMP-2的下調表現。研究TNF-α是否透過活化NF-κB調控EZH2表達，運用NF-κB活性抑制劑(Bay11-7082) 處理細胞後，抑制TNF-α上調的EZH2 mRNA和蛋白質表現。SIRT1為組蛋白去乙醯酶，藉由組蛋白去乙醯化調控目標基因表現，也有研究報導會調節EZH2蛋白質乙醯化而調控EZH2蛋白質穩定性。數據顯示，TNF-α抑制SIRT1活性而增加H3K14組蛋白乙醯化，當細胞轉染使SIRT1過表達可抑制TNF-α上調的EZH2 mRNA和蛋白質表現，以及TIMP-2表現上調。顯示TNF-α誘導EZH2轉錄活性增加是受到TNF-α誘導NF-κB活化及SIRT1活性抑制調控。然而，Cycloheximide(CHX) 研究中顯示，TNF-α誘導下會降低EZH2蛋白質穩定性，進一步研究發現是TNF-α抑制SIRT1而上調β-TrCP表達，進而降低TNF-α誘導之EZH2蛋白質穩定性。綜合上述，本研究指出在人類真皮纖維母細胞(CCD-966SK)，TNF-α上調EZH2基因表達係透過NF-κB轉錄活性和H3K14組蛋白乙醯化，進一步EZH2抑制TIMP-2基因表達係透過組蛋白甲基化。同時，TNF-α會抑制SIRT1去乙醯酶活性，上調β-TrCP並靶向EZH2，使其泛素化而被降解。.
電子資源:	電子資源
館藏註:	(平裝)

人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分子機制研究= Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts/
林育賢

人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分子機制研究= Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts/ Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts林育賢 - [高雄市]: [撰者], 民111 - 77葉: 圖; 30公分

指導教授: 陳瑩容.

碩士論文--高雄醫學大學香粧品學系碩士班.

參考書目：葉.

中文摘要 I

慢性傷口中的發炎因子TNF-α調控金屬蛋白酶組織抑制劑(TIMPs) 活性，延遲傷口癒合過程。TNF-α活化轉錄因子NF-κB調控目標基因表達外，TNF-α也被報導調控EZH2組蛋白甲基轉移酶表現，但尚未有研究釐清在皮膚細胞中TNF-α對EZH2和TIMPs的調控機轉。研究中TNF-α誘導EZH2和TIMP-2 mRNA和蛋白質表現上升。探討TNF-α是否透過EZH2下調TIMP-2表現，細胞處理EZH2甲基轉移酶抑制劑(GSK126)，當EZH2活性受抑制會回復TNF-α對TIMP-2的下調表現。研究TNF-α是否透過活化NF-κB調控EZH2表達，運用NF-κB活性抑制劑(Bay11-7082) 處理細胞後，抑制TNF-α上調的EZH2 mRNA和蛋白質表現。SIRT1為組蛋白去乙醯酶，藉由組蛋白去乙醯化調控目標基因表現，也有研究報導會調節EZH2蛋白質乙醯化而調控EZH2蛋白質穩定性。數據顯示，TNF-α抑制SIRT1活性而增加H3K14組蛋白乙醯化，當細胞轉染使SIRT1過表達可抑制TNF-α上調的EZH2 mRNA和蛋白質表現，以及TIMP-2表現上調。顯示TNF-α誘導EZH2轉錄活性增加是受到TNF-α誘導NF-κB活化及SIRT1活性抑制調控。然而，Cycloheximide(CHX) 研究中顯示，TNF-α誘導下會降低EZH2蛋白質穩定性，進一步研究發現是TNF-α抑制SIRT1而上調β-TrCP表達，進而降低TNF-α誘導之EZH2蛋白質穩定性。綜合上述，本研究指出在人類真皮纖維母細胞(CCD-966SK)，TNF-α上調EZH2基因表達係透過NF-κB轉錄活性和H3K14組蛋白乙醯化，進一步EZH2抑制TIMP-2基因表達係透過組蛋白甲基化。同時，TNF-α會抑制SIRT1去乙醯酶活性，上調β-TrCP並靶向EZH2，使其泛素化而被降解。.

(平裝)Subjects--Index Terms:

人類真皮纖維母細胞.

人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分子機制研究= Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts/
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245 1 0 $a 人類真皮纖維母細胞中TNF-α調控SIRT1/EZH2/TIMP-2的分子機制研究= $b Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts/ $c 林育賢
246 1 1 $a Studies on the molecular mechanisms of TNF-α-modulated SIRT1/EZH2/TIMP-2 axis in human dermal fibroblasts
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500 $a 學年度: 110.
502 $a 碩士論文--高雄醫學大學香粧品學系碩士班.
504 $a 參考書目：葉.
505 0 # $a 中文摘要 I
520 3 $a 慢性傷口中的發炎因子TNF-α調控金屬蛋白酶組織抑制劑(TIMPs) 活性，延遲傷口癒合過程。TNF-α活化轉錄因子NF-κB調控目標基因表達外，TNF-α也被報導調控EZH2組蛋白甲基轉移酶表現，但尚未有研究釐清在皮膚細胞中TNF-α對EZH2和TIMPs的調控機轉。研究中TNF-α誘導EZH2和TIMP-2 mRNA和蛋白質表現上升。探討TNF-α是否透過EZH2下調TIMP-2表現，細胞處理EZH2甲基轉移酶抑制劑(GSK126)，當EZH2活性受抑制會回復TNF-α對TIMP-2的下調表現。研究TNF-α是否透過活化NF-κB調控EZH2表達，運用NF-κB活性抑制劑(Bay11-7082) 處理細胞後，抑制TNF-α上調的EZH2 mRNA和蛋白質表現。SIRT1為組蛋白去乙醯酶，藉由組蛋白去乙醯化調控目標基因表現，也有研究報導會調節EZH2蛋白質乙醯化而調控EZH2蛋白質穩定性。數據顯示，TNF-α抑制SIRT1活性而增加H3K14組蛋白乙醯化，當細胞轉染使SIRT1過表達可抑制TNF-α上調的EZH2 mRNA和蛋白質表現，以及TIMP-2表現上調。顯示TNF-α誘導EZH2轉錄活性增加是受到TNF-α誘導NF-κB活化及SIRT1活性抑制調控。然而，Cycloheximide(CHX) 研究中顯示，TNF-α誘導下會降低EZH2蛋白質穩定性，進一步研究發現是TNF-α抑制SIRT1而上調β-TrCP表達，進而降低TNF-α誘導之EZH2蛋白質穩定性。綜合上述，本研究指出在人類真皮纖維母細胞(CCD-966SK)，TNF-α上調EZH2基因表達係透過NF-κB轉錄活性和H3K14組蛋白乙醯化，進一步EZH2抑制TIMP-2基因表達係透過組蛋白甲基化。同時，TNF-α會抑制SIRT1去乙醯酶活性，上調β-TrCP並靶向EZH2，使其泛素化而被降解。.
520 3 $a The inflammatory factor TNF-α regulates the activity of tissue inhibitors of metalloproteinases (TIMPs) and delays the wound healing process in chronic wounds. TNF-α activates the transcription factor NF-κB to regulate the expression of target genes. TNF-α has also been reported to regulate the expression of EZH2 histone methyltransferase, but there is no study to clarify the regulation of TNF-α on EZH2 and TIMPs in skin cells molecular mechanism. In our study, TNF-α induced the up regulations of EZH2 and TIMP-2 mRNA and protein levels. Cells were treated with EZH2 methyltransferase inhibitor (GSK126) to investigate whether TNF-α downregulated the expression of TIMP-2 through EZH2. When EZH2 activity was inhibited, the downregulation of TIMP-2 by TNF-α could be restored. Treatment of cells with an inhibitor of NF-κB activity (Bay11-7082) inhibited the expression of EZH2 mRNA and protein up regulated by TNF-α to research whether TNF-α regulated EZH2 expression by activating NF-κB. SIRT1 is a histone deacetylase, which regulates the expression of target genes by histone deacetylation. It has also been reported that it can regulate EZH2 protein acetylation, then affect EZH2 protein stability. The data shows that TNF-α inhibits SIRT1 activity and increases H3K14 histone acetylation. When cells were overexpressed SIRT1, TNF α induced EZH2 mRNA and protein expressions are inhibited and up-regulated TIMP-2 expression. It was shown that the increased transcriptional activity of EZH2 induced by TNF-α was regulated by the activation of NF-κB and the inhibition of SIRT1 activity. However, the Cycloheximide (CHX) study showed that TNF-α-induced EZH2 protein stability was reduced. Further studies found that TNF-α inhibited SIRT1 and up-regulated the expression of β-TrCP, thereby reducing the TNF-α-induced EZH2 protein stability. In summary, our study indicates that TNF-α up-regulates EZH2 gene expression through NF-κB transcriptional activity and H3K14 histone acetylation, and further EZH2 inhibites TIMP-2 gene expression through histone methylation in human dermal fibroblasts (CCD-966SK). At the same time, TNF-α inhibits SIRT1 deacetylase activity, up regulates β-TrCP and targets EZH2 for ubiquitination and degradation..
563 $a (平裝)
653 # # $a 人類真皮纖維母細胞.
653 # # $a TNF-α $a TIMP-2 $a EZH2 $a SIRT1 $a β-TrCP $a human dermal fibroblasts.
856 7 # $u https://handle.ncl.edu.tw/11296/55wba3 $z 電子資源 $2 http