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.
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.
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DOI：
10.1159/000532032
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发表时间：
2023
影响因子：
1.7
通讯作者：
Tulis, David A.
中科院分区：
文献类型：
--
作者：
Williams, Madison D.;Bullock, Michael T.;Johnson, Sean C.;Holland, Nathan A.;Vuncannon, Danielle M.;Oswald, Joani Zary;Adderley, Shaquria P.;Tulis, David A.
关键词：
心血管疾病的特征在于血管平滑肌（VSM）从收缩状态转变为增殖状态。蛋白酶激活受体2（PAR2）参与这种表型转换仍不清楚。我们推测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。大鼠克隆性低（PLo; P3-P6）和高传代（PH1; P10-P15）VSM细胞分别建立作为静止和增殖细胞的模型，基于减少的PKG-1和VASP。蛋白质印迹法测定细胞骨架/收缩蛋白、PAR 2和选择蛋白激酶的表达。在PAR2激动（SLIGRL; 100 nM-10 μ m）加/不加PKA（PKI; 10 μ m）、MEK 1/2（PD98059; 10 μ m）和PI3K（LY294002; 1 μ m）阻断后24 - 72 h测量DNA合成和细胞增殖。与PLo细胞相比，PHi细胞中PKG-1、VASP、SM22 α、钙调蛋白、cofilin和PAR 2减少。PAR2激动后，PLo细胞的DNA合成和细胞增殖增加，但PHi细胞减少。Western分析显示PHi细胞中PKA、MEK 1/2和PI3K相对于PLo细胞减少，激酶阻断揭示PAR 2通过PKA/MEK 1/2控制VSM细胞增殖。研究结果突出了PAR2和PAR2驱动的PKA/MEK 1/2控制VSM细胞生长，并为继续研究PAR2在VSM病理学中的作用提供了证据。
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. 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. 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. 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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DOI：
10.1161/01.atv.20.10.2192
发表时间：
2000-10-01
影响因子：
8.7
作者：
Anderson, PG;Boerth, NJ;Lincoln, TM
通讯作者：
Lincoln, TM
影响因子：
7.3
作者：
Bretschneider, E;Kaufmann, R;Schrör, K
通讯作者：
Schrör, K
影响因子：
5.8
作者：
Jiang S;Tang DD
通讯作者：
Tang DD
DOI：
10.1038/nrd.2017.178
发表时间：
2017-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Hauser AS;Attwood MM;Rask-Andersen M;Schiöth HB;Gloriam DE
通讯作者：
Gloriam DE
影响因子：
4.8
作者：
Albinsson, S;Nordström, I;Hellstrand, P
通讯作者：
Hellstrand, P