- 作者：Xianghong Wu ; whw780@gmail.com ; Lang Li
- 关键词：PPAR纬 ; MMP-2 ; Aortic endothelial cells ; Ras-MEK1/2 signaling pathways ; NF-魏B
- 刊名：International Journal of Cardiology
- 出版年：2012
- 期刊代码：128_01675273
- 类别：med
- 出版时间：28 June, 2012
- 卷：158
- 期：1
- 页码：54-58
- 文件大小：432 K
Objectives
Matrix metalloproteinases (MMPs) play a key role in the pathogenesis of chronic inflammatory disease, such as atherosclerosis. Among MMPs, MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions. Peroxisome proliferator activated receptor-gamma (PPAR纬) ameliorates oxidative stress and the inflammatory response. The aim of the present study was to evaluate the effect of Rosiglitazone on lipopolysaccharide (LPS)-induced MMP-2 activation as well as its possible mechanism.Methods
Primary culture of rat aortic endothelial cells (RAEC) was derived from male Sprague-Dawley rat. MMP-2 activity was assayed by gelatin zymography. Protein expressions were determined by Western Blotting. DNA binding activity of NF-魏B was studied with electrophoretic mobility shift assay.
Results
LPS-induced MMP-2 activity was inhibited by Rosiglitazone (PPAR纬 agonist) in the rat aortic endothelial cells (RAEC). LPS-induced MMP-2 activation was diminished due to exposure to NF-魏B Activation Inhibitor II (JSH-23) or Ras inhibitor, farnesylthiosalicylic acid (FTS). Further study shows that LPS-induced activation of Phospho-Ras homologue gene family, member A (Rho A) and Phospho-mitogen-activated protein kinase kinase 1/2 (MEK1/2) were significantly inhibited by Rosiglitazone. The activation of NF-魏B p65 in the nuclear extract of cells was also significantly suppressed by Rosiglitazone, moreover, the expression of NF-魏B p65 was partly activated by GW9662 (PPAR纬 antagonist). NF-魏B DNA binding activity was also demolished by Rosiglitazone.
Conclusions
Our data shows that PPAR纬 agonist, Rosiglitazone suppresses LPS-activated MMP-2 secretion via Ras-MEK1/2 signaling pathways and NF-魏B activation. PPAR纬 agonist and Ras-MEK1/2 pathway may be another potential therapeutic target for the disease induced by chronic inflammation.