Cyclophilin A Is a Secreted Growth Factor Induced by Oxidative Stress
作者:
Zheng-Gen Jin,
Matthew Melaragno,
Duan-Fang Liao,
Chen Yan,
Judith Haendeler,
Young-Ah Suh,
J. Lambeth,
Bradford Berk,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2000)
卷期:
Volume 87,
issue 9
页码: 789-796
ISSN:0009-7330
年代: 2000
出版商: OVID
关键词: oxidative stress;cyclophilin;secretion;mitogen-activated protein kinase;smooth muscle cells
数据来源: OVID
摘要:
Abstract—Reactive oxygen species have been implicated in the pathogenesis of atherosclerosis, hypertension, and restenosis, in part by promoting vascular smooth muscle cell (VSMC) growth. Many VSMC growth factors are secreted by VSMC and act in an autocrine manner. Here we demonstrate that cyclophilin A (CyPA), a member of the immunophilin family, is secreted by VSMCs in response to oxidative stress and mediates extracellular signal–regulated kinase (ERK1/2) activation and VSMC growth by reactive oxygen species. Human recombinant CyPA can mimic the effects of secreted CyPA to stimulate ERK1/2 and cell growth. The peptidyl-prolyl isomerase activity is required for ERK1/2 activation by CyPA. In vivo, CyPA expression and secretion are increased by oxidative stress and vascular injury. These findings are the first to identify CyPA as a secreted redox-sensitive mediator, establish CyPA as a VSMC growth factor, and suggest an important role for CyPA and enzymes with peptidyl-prolyl isomerase activity in the pathogenesis of vascular diseases.
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