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Protease-Activated Receptor 2 Controls Vascular Smooth Muscle Cell Proliferation in Cyclic AMP-Dependent Protein
Madison D Williams1, Michael T Bullock2, Sean C Johnson3
1Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
Journal of Vascular Research
|October 1, 2023
Summary
Protease-activated receptor 2 (PAR2) influences vascular smooth muscle cell (VSM) proliferation. PAR2 activation promotes proliferation in quiescent cells but inhibits it in proliferative cells, mediated by PKA and MEK1/2 kinases.
Area of Science:
- Vascular Biology
- Cell Signaling
- Cardiovascular Research
Background:
- Cardiovascular disorders involve vascular smooth muscle cell (VSM) transition from contractile to proliferative states.
- The role of Protease-activated receptor 2 (PAR2) in VSM phenotypic conversion is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that PAR2 controls VSM cell proliferation in a phenotype-dependent manner.
- To elucidate the involvement of specific protein kinases in PAR2-mediated VSM cell proliferation.
Main Methods:
- Established rat clonal low (PLo) and high passage (PHi) VSM cells as models of quiescent and proliferative states, respectively.
- Utilized Western blotting to assess protein expression, including PAR2 and key kinases.
- Measured DNA synthesis and cell proliferation following PAR2 agonism with and without kinase inhibitors (PKA, MEK1/2, PI3K).
Main Results:
- PHi cells exhibited reduced levels of PKG-1, VASP, and PAR2 compared to PLo cells.
- PAR2 agonism increased proliferation in PLo cells but decreased it in PHi cells.
- PAR2-mediated VSM cell proliferation was found to be dependent on PKA and MEK1/2 signaling pathways.
Conclusions:
- PAR2 plays a critical role in regulating VSM cell growth in a phenotype-dependent manner.
- PAR2-driven PKA/MEK1/2 signaling is a key mechanism controlling VSM cell proliferation.
- These findings support further investigation of PAR2 in the context of VSM pathologies.
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