Reactive oxygen species-mediated signaling pathways in angiotensin II-induced MCP-1 expression of proximal tubular cells.
Reactive oxygen species-mediated signaling pathways in angiotensin II-induced MCP-1 expression of proximal tubular cells.
复制标题
DOI：
10.1089/ars.2005.7.1261
复制
发表时间：
2005-08
影响因子：
6.6
通讯作者：
Chiaki Tanifuji;Yusuke Suzuki;Wong Mu Geot;S. Horikoshi;T. Sugaya;M. Ruíz-Ortega;J. Egido;Y. Tomino
中科院分区：
文献类型：
--
作者：
Chiaki Tanifuji;Yusuke Suzuki;Wong Mu Geot;S. Horikoshi;T. Sugaya;M. Ruíz-Ortega;J. Egido;Y. Tomino
血管紧张素II（AngII）具有多效性作用，其中最众所周知的是在炎性病变中产生活性氧（ROS）和趋化因子。单核细胞趋化蛋白-1（MCP-1）被认为是肾脏疾病发病机制中的主要趋化因子。我们研究了血管紧张素II诱导的MCP-1表达的信号通路和ROS在小鼠近端肾小管细胞（mProx）中的作用，使用各种抑制剂。此外，我们比较了mProx和系膜细胞（MC）之间的信号通路。在6 h时，血管紧张素II诱导的MCP-1蛋白在mProx中的表达在很大程度上被ROS（N-乙酰半胱氨酸; 82 +/- 14%）、Ras（N-乙酰-S-反式，反式-法呢基-L-半胱氨酸; 82 +/- 13%）和核因子-κ B（NF-κ B）（parthenocyte; 89 +/- 7.9%）抑制剂阻断。AT 1受体（AT 1 R）（奥美沙坦; 41 +/- 12%）和AT 2 R（PD 123319; 24 +/- 11%）拮抗剂均部分阻断MCP-1表达。此外，有丝分裂原活化蛋白激酶（MAPK）途径也参与该蛋白的表达，但它对ROS/Ras途径的依赖性较低。在MC中，蛋白激酶（calphostin C; 84 +/- 2.8%）和NF-κ B（89 +/- 1.4%）抑制剂比ROS/Ras抑制剂（1.0 +/- 0.9/29 +/- 9.5%）更强地减弱急性AngII诱导的MCP-1表达。MAPK信号通路，尤其是p38 MAPK，在MC中的参与程度高于mProx。AT 1 R（69 +/- 8.6%）和AT 2 R（57 +/- 21%）拮抗剂也被阻断。我们认为，虽然NF-κ B活化具有关键作用，但mProx和MC之间的信号通路是不同的。mProx中ROS介导的信号传导可能比MC中的信号传导对AngII诱导的炎症反应有更大的贡献。
Angiotensin II (AngII) has pleiotropic effects, the most well known of which is the generation of reactive oxygen species (ROS) and chemokines in inflammatory lesions. Monocyte chemoattractant protein-1 (MCP-1) is considered a major chemokine in the pathogenesis of kidney diseases. We examined signaling pathways of AngII-induced MCP-1 expression and the role of ROS in the murine proximal tubular cells (mProx) using various inhibitors. Furthermore, we compared the signaling pathways between mProx and mesangial cells (MC). AngII-induced MCP-1 protein expression in mProx at 6 h was largely blocked by ROS (N-acetylcysteine; 82 +/- 14%), Ras (N-acetyl-S-trans,trans-farnesyl-L-cysteine; 82 +/- 13%), and nuclear factor-kappaB (NF-kappaB) (parthenolide; 89 +/- 7.9%) inhibitors. Both AT1 receptor (AT1R) (Olmesartan; 41 +/- 12%) and the AT2R (PD123319; 24 +/- 11%) antagonists partially blocked the MCP-1 expression. Furthermore, mitogen-activated protein kinase (MAPK) pathways were also implicated in this protein expression, but it is less dependent on ROS/Ras pathways. In MC, protein kinase (calphostin C; 84 +/- 2.8%) and NF-kappaB (89 +/- 1.4%) inhibitors attenuated acute AngII-induced MCP-1 expression stronger than ROS/Ras inhibitors (1.0 +/- 0.9/29 +/- 9.5%). MAPK pathways, especially p38 MAPK, were involved in MC more than in mProx. AT1R (69 +/- 8.6%) and AT2R (57 +/- 21%) antagonists also were blocked. We suggested that, although NF-kappaB activation has a critical role, signaling pathways are different between mProx and MC. ROS-mediated signaling in mProx may have more contribution to AngII-induced inflammatory responses than to those in MC.