Shi Rui-Zhen, Wang Ji-Chang, Huang Song-Hua, Wang Xiao-Jun, Li Qing-Ping
Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Exp Cell Res. 2009 Jan 1;315(1):10-5. doi: 10.1016/j.yexcr.2008.09.024. Epub 2008 Oct 11.
Mesenchymal stem cells (MSCs) transplantation has been proposed as a promising means for ischemic heart disease. Vascular endothelial growth factor (VEGF) has been demonstrated to play an important role in MSCs transplantation. Angiotensin II (AngII), the most important effector peptide of the renin-angiotensin system (RAS), is also an angiogenesis factor. However, the effects of AngII on VEGF expression in MSCs and the related signaling cascades were unknown. In this experiment, we first demonstrated that incubation of MSCs with AngII-induced a rapid increase in VEGF mRNA expression and protein synthesis. However, these effects were abolished by prior treatment with AngII type 1 (AT(1)) receptor antagonist losartan while not AngII type 2 (AT(2)) receptor antagonist PD123319. The addition of either the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 or Akt inhibitor LY294002 also led to a marked inhibition of the AngII-induced VEGF mRNA and protein production. Taken together, these results suggested that AngII stimulated the synthesis of VEGF in MSCs through ERK1/2 and Akt pathway via AT(1) receptor.
间充质干细胞（MSCs）移植已被认为是治疗缺血性心脏病的一种有前景的方法。血管内皮生长因子（VEGF）已被证明在MSCs移植中起重要作用。血管紧张素II（AngII）是肾素-血管紧张素系统（RAS）最重要的效应肽，也是一种血管生成因子。然而，AngII对MSCs中VEGF表达及相关信号级联反应的影响尚不清楚。在本实验中，我们首先证明用AngII孵育MSCs可导致VEGF mRNA表达和蛋白合成迅速增加。然而，这些效应在用1型AngII（AT(1)）受体拮抗剂氯沙坦预先处理后被消除，而2型AngII（AT(2)）受体拮抗剂PD123319则无此作用。添加细胞外信号调节激酶1/2（ERK1/2）抑制剂U0126或Akt抑制剂LY294002也会显著抑制AngII诱导的VEGF mRNA和蛋白产生。综上所述，这些结果表明AngII通过AT(1)受体经ERK1/2和Akt途径刺激MSCs中VEGF的合成。
