根據流行病學上的研究指出，慢性發炎經常伴隨著許多與年齡老化有關的疾病，例如：神經退化、動脈硬化症、第二型糖尿病與類風濕性關節炎，進而增加死亡的危險性。已知轉錄因子CCAAT/enhancer binding protein (CEBPD) 參與許多發炎相關基因的調控。雖然許多基因參與在阿茲罕默症的形成中之訊息傳遞，及生理上扮演重要的角色已被報導，但其確切的致病機制卻仍不清楚。已知在阿茲海默症的形成過程中，總會伴隨著有發炎反應的產生與神經細胞的退化與萎縮。已有文獻指出在阿茲海默症病人中，可以觀察到CEBPD蛋白質表現量增加。然而，此CEBPD的增加是否在阿茲海默症的形成過程扮演任何角色目前尚未清楚。根據在人類星細胞中增加CEBPD表達所得的微陣列資料分析結果，發現許多與發炎有關的基因受到活化，本論文主要針對CEBPD可以活化的一個重要發炎相關基因pentraxin-3 (PTX3) 之轉錄機制進行研究。另外，為了研究CEBPD是否可以直接調控PTX3基因轉錄，我也利用自行設計用來預測CEBPD結合位的軟體(Prediction of CEBPD-Binding Motif, PCDBM) 分析 PTX3 基因啟動區序列上具有5個可能的CEBPD專一結合位置。進一步地，利用活體外DNA結合實驗證實其中的 site 1及site 5 具有較高之CEBPD結合能力，此結果符合 PCDBM 的預期結果。後續更透過報導基因分析方法證實此兩個CEBPD結合位置對於CEBPD活化 PTX3基因轉錄扮演著重要的角色。總結前述，透過微陣列分析人類星細胞中的基因表現程度，顯示PTX3 基因轉錄受到CEBPD調控。再經由分子生物學的實驗進而驗證出 PTX3 基因啟動子上最佳之CEBPD結合位置，此結果與PCDBM的預期結果相符。這些研究結果顯示CEBPD可以增加星細胞中的PTX3 基因轉錄作用，而此一個由內而外的訊息傳遞路徑可能作用於神經細胞而參與阿茲海默症的形成過程。

Epidemiologic studies suggest that chronic inflammation in aging is related to age-associated disorders, such as neuron degeneration, atherosclerosis, type II diabetes and rheumatoid arthritis, and enhanced mortality risk. There are many CEBPD-regulated genes respond to inflammatory stimulation. Even though the models of signaling transduction in Alzheimer's disease (AD) had been reported, the linkages of these models remain uncertain. Previous studies have shown that the process of neuron degeneration in AD goes along with inflammation caused by immune responses. Up-regulation of CEBPD was observed in AD. However, the biological function of CEBPD remains unknown in AD. According to our microarray results, an important inflammatory marker, pentraxin-3 (PTX3), was identified. To characterize whether CEBPD can directly regulate PTX3 transcription through promoter regulation, the program of Prediction of CEBPD-Binding Motif (PCDBM) was generated to predict the putative CEBPD-binding motifs. On the other hand, an in vitro DNA binding assay showed a coincident result with PCDBM, suggesting that the site 1 and site 5 of putative CEBP motifs on PTX3 promoter have high affinity for CEBPD-binding. Moreover, the importance of site 1 and site 5 for the CEBPD-regulated PTX3 transcriptional activation was verified with reporter assays. Taken together, PTX3 was identified as a CEBPD-responsive gene through the global profiling in U373MG cells. Moreover, the molecular biology evidence demonstrated that the important CEBPD-responsive motifs on PTX3 promoter, which is coincident with the PCDBM program. These results suggested that CEBPD can activate PTX3 transcription to generate an inside-out signal, which may contribute to the communication between astrocytes and neuron in AD.

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