Protease-Activated Receptor 2 Controls Vascular Smooth Muscle Cell Proliferation in Cyclic AMP-Dependent Protein Kinase/Mitogen-Activated Protein Kinase Kinase 1/2-Dependent Manner.

IF 1.8 4区医学 Q3 PERIPHERAL VASCULAR DISEASE Journal of Vascular Research Pub Date : 2023-01-01 Epub Date: 2023-09-29 DOI:10.1159/000532032

Madison D Williams, Michael T Bullock, Sean C Johnson, Nathan A Holland, Danielle M Vuncannon, Joani Zary Oswald, Shaquria P Adderley, David A Tulis

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引用次数: 1

Abstract

Introduction: Cardiovascular disorders are characterized by vascular smooth muscle (VSM) transition from a contractile to proliferative state. Protease-activated receptor 2 (PAR2) involvement in this phenotypic conversion remains unclear. We hypothesized that PAR2 controls VSM cell proliferation in phenotype-dependent manner and through specific protein kinases.

Methods: Rat clonal low (PLo; P3-P6) and high passage (PHi; P10-P15) VSM cells were established as respective models of quiescent and proliferative cells, based on reduced PKG-1 and VASP. Western blotting determined expression of cytoskeletal/contractile proteins, PAR2, and select protein kinases. DNA synthesis and cell proliferation were measured 24-72 h following PAR2 agonism (SLIGRL; 100 nM-10 μm) with/without PKA (PKI; 10 μm), MEK1/2 (PD98059; 10 μm), and PI3K (LY294002; 1 μm) blockade.

Results: PKG-1, VASP, SM22α, calponin, cofilin, and PAR2 were reduced in PHi versus PLo cells. Following PAR2 agonism, DNA synthesis and cell proliferation increased in PLo cells but decreased in PHi cells. Western analyses showed reduced PKA, MEK1/2, and PI3K in PHi versus PLo cells, and kinase blockade revealed PAR2 controls VSM cell proliferation through PKA/MEK1/2.

Discussion: Findings highlight PAR2 and PAR2-driven PKA/MEK1/2 in control of VSM cell growth and provide evidence for continued investigation of PAR2 in VSM pathology.

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蛋白酶激活受体2以环腺苷酸依赖性蛋白激酶/有丝分裂原激活蛋白激酶1/2依赖性方式控制血管平滑肌细胞增殖。

引言：心血管疾病的特点是血管平滑肌从收缩状态转变为增殖状态。蛋白酶激活受体2（PAR2）参与这种表型转化尚不清楚。我们假设PAR2以表型依赖的方式并通过特异性蛋白激酶控制VSM细胞增殖。方法：在PKG-1和VASP减少的基础上，建立大鼠克隆性低（PLo；P3-P6）和高传代（PHi；P10-P15）VSM细胞分别作为静止和增殖细胞的模型。蛋白质印迹测定细胞骨架/收缩蛋白、PAR2和选择蛋白激酶的表达。在PAR2激动剂（SLIGRL；100nM-10μm）与/不与PKA（PKI；10μm）、MEK1/2（PD98059；10μm）和PI3K（LY294002；1μm）阻断后24-72小时测量DNA合成和细胞增殖。结果：与PLo细胞相比，PHi细胞中PKG-1、VASP、SM22α、钙蛋白酶、辅因子和PAR2降低。PAR2激动剂作用后，PLo细胞中的DNA合成和细胞增殖增加，但PHi细胞中的减少。Western分析显示，与PLo细胞相比，PHi细胞中的PKA、MEK1/2和PI3K降低，激酶阻断显示PAR2通过PKA/MEK1/2控制VSM细胞增殖。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Vascular Research 医学-生理学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.