期刊
LIFE SCIENCES
卷 91, 期 5-6, 页码 172-177出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2012.06.033
关键词
Uremic toxin; Tryptophan metabolite; Chronic kidney disease; Reactive oxygen species; Arteriosclerosis
资金
- Grants-in-Aid for Scientific Research [12F02089] Funding Source: KAKEN
Aims: Indoxyl sulfate, a uremic toxin, is considered a risk factor for arteriosclerosis in patients with chronic kidney disease (CKD). We previously reported the actions of indoxyl sulfate including crosstalk with platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs). The present study examines whether indoxyl sulfate enhances angiotensin 11 (Ang II) signaling because serum levels of Ang II are elevated in patients with CKD. Main methods: The effect of indoxyl sulfate and Ang II on phosphorylation of ERK and epidermal growth factor receptor (EGFR), and migration were determined using VSMCs. The expression of EGFR was determined using not only VSMCs but also artery of normal, uremic, and indoxyl sulfate-administrated uremic rats. Key findings: Ang II-dependent phosphorylation of ERK and EGFR, and migration of VSMCs were augmented by a prior 24-h incubation with indoxyl sulfate even in the absence of indoxyl sulfate during Ang II stimulation. The expression of EGFR was increased in indoxyl sulfate-stimulated cultured VSMCs. In arterial VSMCs of rats, serum levels of indoxyl sulfate reflected the expression level of EGFR. The upregulated EGFR expression by indoxyl sulfate was suppressed by the antioxidant, N-acetylcysteine. An EGFR inhibitor, AG1478, repressed the enhancement of Ang II-induced cellular effects by indoxyl sulfate. Taken together, these findings indicate that indoxyl sulfate enhances Ang II signaling through reactive oxygen species-induced EGFR expression. Significance: The actions of indoxyl sulfate including crosstalk with Ang II signaling may be closely involved in the pathogenesis of CKD associated with arteriosclerosis. (C) 2012 Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据