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

被引:1
|
作者
Williams, Madison D. [1 ]
Bullock, Michael T. [2 ]
Johnson, Sean C. [3 ]
Holland, Nathan A. [4 ]
Vuncannon, Danielle M. [5 ]
Oswald, Joani Zary
Adderley, Shaquria P. [6 ,7 ]
Tulis, David A. [1 ]
机构
[1] East Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC 27858 USA
[2] Edward Via Coll Osteopath Med, Carolinas Campus, Spartanburg, SC USA
[3] Indiana Univ Sch Med, Dept Internal Med Pediat, Indianapolis, IN USA
[4] Texas Tech Univ, Hlth Sci Ctr El Paso, Dept Med Educ, El Paso, TX USA
[5] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA
[6] East Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC USA
[7] Touro Univ Nevada, Basic Sci Dept, Henderson, NV USA
关键词
Proliferation; Protease-activated receptor 2; Protein kinase; Vascular smooth muscle cell; Cardiovascular disease; BAY; 41-2272; EXPRESSION; MIGRATION; DIFFERENTIATION; SENESCENCE; PHENOTYPE; CONDUIT; PATHWAY; ROLES; PAR-2;
D O I
10.1159/000532032
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 (P-Lo; P3-P6) and high passage (P-Hi; 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 mu<sc>m</sc>) with/without PKA (PKI; 10 mu<sc>m</sc>), MEK1/2 (PD98059; 10 mu<sc>m</sc>), and PI3K (LY294002; 1 mu<sc>m</sc>) blockade. Results: PKG-1, VASP, SM22 alpha, calponin, cofilin, and PAR2 were reduced in P-Hi versus P-Lo cells. Following PAR2 agonism, DNA synthesis and cell proliferation increased in P-Lo cells but decreased in P-Hi cells. Western analyses showed reduced PKA, MEK1/2, and PI3K in P-Hi versus P-Lo 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.
引用
收藏
页码:213 / 226
页数:14
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