Store-operated Ca(2+) entry is not essential for PDGF-BB induced phenotype modulation in rat aortic smooth muscle.
Suppression of smooth muscle cell (SMC) differentiation marker genes is central to SMC phenotype modulation during vasculo-proliferative diseases such as atherosclerosis and restenosis. Upregulation of the intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) is integral for mitogen-induced suppression of SMC marker genes and post-angioplasty restenosis. Modulation of SMC marker gene expression has been observed following Ca(2+) influx from multiple sources, however, it is unknown whether upregulation of K(Ca)3.1 and/or suppression of SMC differentiation genes is dependent on a Ca(2+) mediated mechanism. The purpose of this study was to determine the dependence of mitogen-induced SMC phenotype modulation on store-operated Ca(2+) entry (SOCE). In growth-arrested, differentiated rat aortic SMCs, platelet-derived growth factor-BB (PDGF-BB) augmented SOCE. However, PDGF-BB induced upregulation of K(Ca)3.1 and downregulation of the SMC marker gene smooth muscle myosin heavy chain (SMMHC) and myocardin was not dependent on SOCE. Co-treatment with the iPLA2 inhibitor bromoenol lactone (BEL) inhibited the effects of PDGF-BB on SMC phenotype modulation and SOCE. Our results indicate SOCE is not required for PDGF-BB induced phenotype modulation in rat aortic SMCs. Rather, we implicate a novel BEL-sensitive mechanism which regulates both SOCE and phenotype modulation, independently.
Emter
Craig A
CA
Department of Biomedical Science, University of Missouri-Columbia, 1600 E. Rollins, W160 Veterinary Medicine, Columbia, MO 65211, United States. emterc@missouri.edu
Bowles
Douglas K
DK
D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C491575:Kcnn4 protein, rat; D009281:Naphthalenes; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011753:Pyrones; D000077214:Becaplermin; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D002118:Calcium