Although peroxisome proliferator-activated receptor (PPAR) is widely expressed in many tissues, the role of PPAR is poorly understood. In this study, we report that PPAR was up-regulated in vascular smooth muscle cells (VSMC) during vascular lesion formation. By using Northern blot analysis, we demonstrated that PPAR was increased by 3-4-fold in VSMC treated with platelet-derived growth factor (PDGF) (20ng/ml). In addition, PDGF-induced PPAR mRNA expression neither needs de novo protein synthesis nor affects the stability of PPAR mRNA in VSMC. Preincubation of VSMC with phosphatidylinositol 3-kinase inhibitor (LY294002, 50mol/liter) or infection of VSMC with an adenovirus carrying the gene for a dominant negative form of Akt abrogated PDGF-induced PPAR mRNA expression, suggesting that phosphatidylinositol 3-kinase/Akt signaling pathway is involved in the regulation of PDGFinduced PPAR mRNA expression in VSMC. To explore the role of PPAR in VSMC, we generated rat vascular smooth muscle cells (A7r5) stably overexpressing PPAR and the control green fluorescent protein. Overexpression of PPAR in VSMC increased post-confluent cell proliferation by increasing the cyclin A and CDK2 as well as decreasing p57kip2. Taken together, the results suggest that PPAR plays an important role in the pathology of diseases associated with VSMC proliferation, such as primary atherosclerosis and restenosis.

Vascular diseases such as atherosclerosis are characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal lining. The intimal VSMCs exhibit an increased expression of peroxisome proliferator-activated receptor (PPAR), and the administration of pharmacological PPAR agonists attenuates vascular lesion formation. The factors that regulate PPAR expression in the vasculature are poorly defined. Here we report that platelet-derived growth factor (PDGF) upregulates PPAR by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathway. Using Northern-blotting and Western-blotting analyses, we observed that the levels of PPAR mRNA and protein were increased by 2-to 3.5-fold in human aortic smooth muscle cells (HASMCs) treated with PDGF (20ng/mL). This was abolished by preincubation of HASMCs with a PI3-kinase inhibitor (LY294002, 50mol/L), and partially inhibited by a MEK1 inhibitor (U0126, 10mol/L), but not affected by a p38 kinase inhibitor (SB202190, 10mol/L). In addition, overexpression of the dominant-negative p85 subunit of PI3-kinase or Akt proteins blocked the PDGF-induced PPAR expression. Taken together, our results suggest that PDGF induces PPAR expression in VSMCs by a PI3-kinase/Akt signaling pathway. The characterization of factors and signaling pathways that modulate PPAR expression in VSMCs may have important implications for understanding the pathogenesis of vascular diseases.

目的：通过观察IFN-alb对肝星状细胞（HSC）形态和表达CIGF的影响，探讨IFN-alb在治疗纤维化中的作用机制。方法：采用体外培养大鼠肝星状细胞，分别加入IFN-alb、TGF-β1，观察肝星状细胞的形态学及CTGF表达的改变。结果：透射电镜观察到IFN-alb作用组肝星状细胞有明显的凋亡现象发生；RT-PCR观察到正常组和1GF-β1诱导肝星状细胞表达的CTGF mRNA随IFN-alb的作用而减少。结论：IFN-alb对肝星状细胞表达CT-GF的抑制作用机制可能是通过诱导肝星状细胞凋亡和抑制TGF-β1诱导肝星状细胞表达CTGF。