期刊
CELLULAR SIGNALLING
卷 18, 期 10, 页码 1695-1701出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2006.01.009
关键词
vascular smooth muscle; G protein coupled receptor; restenosis; lysophosphatidic acid; migration; proliferation; mitogen
类别
Many G protein-coupled receptors can couple to multiple G proteins to convey their intracellular signaling cascades. The receptors for lysophosphatidic acid (LPA) possess this ability. LPA receptors are important mediators of a wide variety of biological actions including cell migration, proliferation and survival which are processes that can all have a considerable impact on vascular smooth muscle (VSM) and blood vessels. To date, confirmation of G proteins involved has mostly relied on the inhibition of Gi-mediated signaling via pertussis toxin (PTx). We were interested in the specific involvement of LPA-Gq-mediated signaling therefore we isolated aorta VSM cells (VSMCs) from transgenic mice that express a peptide inhibitor of Gq, GqI, exclusively in VSM. We detected both LPA1 and LPA2 receptor expression in mouse VSM whereas LPA1 and LPA3 were expressed in rat VSM. SM22-GqI did not alter LPA-induced migration but it was sufficient to attenuate LPA-induced proliferation. GqI expression also attenuated LPA-induced FRK1/2 and Akt activation by 40-50%. To test the feasibility of this peptide as a potential therapeutic agent, we also generated adenovirus encoding the GqI. Transient expression of GqI was capable of inhibiting both LPA-induced migration and proliferation of VSMCs isolated from rat and mouse. Furthermore, ERK activation in response to LPA was also attenuated in VSMCs with Adv-GqI. Therefore, LPA receptors couple to Gq in VSMC and mediate migration and proliferation which may be mediated through activation of ERK1/2 and Akt. Our data also suggest that both chronic and transient expression of the GqI peptide is an effective strategy to lower Gq-mediated LPA signaling and may be a successful therapeutic strategy to combat diseases with enhanced VSM growth such as occurs following angioplasty or stent implantation. (c) 2006 Elsevier Inc. All rights reserved.
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