Studies on Signaling Pathway of CTGF-Induced Cyclooxygenase-2 Expression in Rat C6 Glioma Cells

• Main Authors: Chia-Wei Liang, 梁家瑋
• Other Authors: Chien-Huang Lin
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/42264076005140339835

碩士 === 臺北醫學大學 === 醫學科學研究所 === 98 === In CNS trauma process, Connective tissue growth factor (CTGF) regulates a wide range of cellular process, including angiogenesis and reactive gliosis. There is growing evidence that increased expression of cyclooxygenase-2 (COX-2) in acute CNS injury is key event in the pathogenesis of CNS injury. However, the molecular mechanisms underlying CTGF-induced COX-2 expression are still undefined In this study, we investigated the involvement of the ERK, JNK, IκBkinase α/β (IKKα/β), and NF-κB signaling pathways in CTGF-induced COX-2 expression in rat C6 glioma cells. Treatment of C6 glioma cell with CTGF caused not only increased COX-2 expression in a concentration- and time-dependent manner but also increased COX-2 -luciferase activity. Treatment of C6 glioma cells with PD98059 (a MEK inhibitor) or SP600125 (a JNK inhibitor) inhibited CTGF-induced COX-2 expression, COX-2-luciferase activity and κB-luciferase acivity. The CTGF-mediated increases in IKKα/β phosphorylation and κB-luciferase activity were inhibited by PD98059 and SP600125. Stimulation of cells with CTGF caused an increase in ERK and JNK phosphorylation in a dose-dependent manner. In addition, treatment of C6 glioma cells with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor), inhibited CTGF-induced COX-2 expression. The CTGF-induced increase in COX-2-expression or COX-2-luciferase activity were also blocked by the dominant negative of IκBαM and κB-mutanted-COX-2 promoter. Treatment of C6 glioma cells with CTGF induced IKKα/β, IκBα phosphorylation, and IκBα?? degradation. Moreover, CTGF increased binding of p65 and p50 to COX-2 promoter region. Taken together, these results suggest that the JNK- and ERK-dependent/ IKKα/β/ IκBα and NF-κB signaling pathway play important role in CTGF-induced COX-2 expression in C6 glioma cells.