Involvement of S6 kinase and p38 mitogen activated protein kinase pathways in strain-induced alignment and proliferation of bovine aortic smooth muscle cells.
Bovine aortic smooth muscle cell (SMC) phenotype can be altered by physical forces. This has been demonstrated by cyclic strain-induced changes in proliferation and alignment. However, the intracellular coupling pathways remain ill defined. In the present study, we examined whether the p38 and S6 kinase pathway were involved in the mitogenic and morphological changes seen in SMCs exposed to cyclic strain. We seeded bovine aortic SMCs on silastic membranes that were deformed with 150-mmHg vacuum. Cyclic strain induced both alignment and proliferation of SMCs. SB202190, a specific inhibitor of p38, hindered SMC alignment, but not proliferation. Rapamycin, a specific inhibitor of the mTOR-S6 kinase pathway, attenuated strain-induced proliferation, but not alignment. Peak activation of p38 and S6 kinase was 351 +/- 76.9% at 5 min and 363 +/- 56.2% at 60 min compared with static control, respectively (P < 0.05). The results suggest that strain-induced SMC alignment is dependent on activation of p38, but not S6 kinase. Strain induced SMC proliferation is S6 kinase, but not p38 activation, dependent.
Li
Wei
W
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Chen
Quanhai
Q
Mills
Ira
I
Sumpio
Bauer E
BE
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D002417:Cattle; D002455:Cell Division / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007166:Immunosuppressive Agents; D011725:Pyridines; D014157:Transcription Factors; D019893:Ribosomal Protein S6 Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D020123:Sirolimus