Characterization of CEBPD elevating PTX3 expression in astrocytes

• Main Authors: Chun-Pei Cheng, 程俊培
• Other Authors: Ju-Ming Wang
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/69346700325786999882

碩士 === 國立成功大學 === 生物資訊研究所 === 97 === 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.