Mechanisms of cyclooxygenase2 expression-induced by oxidized-LDL in VSMC

氧化LDL诱导VSMC中环氧合酶2表达的机制

• 批准号: 13670736
• 负责人: YAMAKAWA Tadashi
• 金额: $ 2.3万
• 依托单位: Yokohama City University Hospital
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670736/
• 关键词: Cyclooxygenase2; p42; 44MAPK; p38MAPK; Atherosclerosis; VSMC; cyclooxygenase2; cyclooxygenase 2

In 2001, proliferation of vascular smooth muscle cells (VSMC) were found to be mediated through cyclooxygenase 2 (COX2) expression-induced by Oxidized LDL. We also identified that COX2 expression was dependent on the activation of p42/44MAPK and p38MAPK. In 2002, in order to elucidate the regulation of transcription of COX2 and novel pathways besides MAPKs, we performed following experiments. First, we examined the role of p42/44MAPK and p38MAPK on cox2 mRNA expression. We identified that p42/44MAPK was related with transcription of cox2 and p38MAPK was associated with the stabilization of cox2 mRNA. Second, Dr Eguchi found that mRNA expression of helix-loop helix Id3 aw well as p21WAP/Cip1 and p27Kip1 were enhanced by oxidized-LDL stimulation in VSMC. It is very interesting that all of them were cell cycle related genes. Therefore, we need to do further investigation of the signaling pathway of these genes-induced by oxidized-LDL to identify the mechanisms of growth of VSMC.

2001年，人们发现血管平滑肌细胞（VSMC）的增殖是通过氧化LDL诱导的环氧合酶2（COX2）表达来介导的。我们还发现 COX2 表达依赖于 p42/44MAPK 和 p38MAPK 的激活。 2002年，为了阐明COX2的转录调控以及MAPK之外的新途径，我们进行了以下实验。首先，我们检查了 p42/44MAPK 和 p38MAPK 对 cox2 mRNA 表达的作用。我们发现p42/44MAPK与cox2的转录相关，p38MAPK与cox2 mRNA的稳定相关。其次，Eguchi 博士发现 VSMC 中氧化 LDL 刺激增强了螺旋环螺旋 Id3 aw 以及 p21WAP/Cip1 和 p27Kip1 的 mRNA 表达。非常有趣的是，它们都是细胞周期相关的基因。因此，我们需要进一步研究氧化LDL诱导这些基因的信号通路，以明确VSMC生长的机制。

项目成果

T. Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinesis 1/2 through Reactive Oxygen Species in Rat Vascular Smooth Muscle Cells"Arteriosclerosis, Thrombosis, and Vascular Biology 22. 752-758 (2002)

T. Yamakawa 等人：“溶血磷脂酰胆碱通过大鼠血管平滑肌细胞中的活性氧激活细胞外信号调节运动 1/2”动脉硬化、血栓形成和血管生物学 22. 752-758 (2002)

Y Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinases 1/2 through"Arteriosclerosis, Thrombosis, and Vascular Biology. 22. 752-758 (2002)

Y Yamakawa 等人：“溶血磷脂酰胆碱通过”动脉硬化、血栓形成和血管生物学激活细胞外信号调节激酶 1/2。

T Yamakawa et al.: "Lysophosphatidylcholine Inhibits Insulin-Induced Akt Activation Through Protein"Hypertension. 39. 508-512 (2002)

T Yamakawa 等人：“溶血磷脂酰胆碱通过蛋白质抑制胰岛素诱导的 Akt 激活”高血压。

T Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinases 1/2"Arteriosclerosis, Thrombosis, and Vascular Biology. 22. 752-758 (2002)

T Yamakawa 等人：“溶血磷脂酰胆碱激活细胞外信号调节激酶 1/2”动脉硬化、血栓形成和血管生物学。

T. Yamakasa et al.: "Insulin-Induced Akt Activation Through Protein Kinase C-α in Vascular Smooth Muscle Cells"Hypertension 39. 508-512 (2002)

T. Yamakasa 等人：“血管平滑肌细胞中通过蛋白激酶 C-α 诱导的胰岛素诱导 Akt 激活”高血压 39. 508-512 (2002)