Frequency-dependent phenotype modulation of vascular smooth muscle cells under cyclic mechanical strain.
Phenotype transformation of vascular smooth muscle cells (VSMCs) is known to be modulated by mechanical strain. The present study was designed to investigate how different frequencies of mechanical strain affected VSMC phenotype. VSMCs were subjected to the strains of 10% elongation at 0, 0.5, 1 and 2 Hz for 24 h using a Flexercell strain unit. VSMC phenotype was assessed by cell morphology, measurement of two-dimensional cell area, Western blotting for protein and RT-PCR for mRNA expression of differentiation markers. Possible protein kinases involved were evaluated by Western blotting with their specific antibodies. The strains at certain frequencies could induce a contractile morphology in VSMC with almost perpendicular alignment to the strain direction. The strains also regulated protein and mRNA expression of several differentiation markers, as well as the activation of extracellular signal-regulated kinases (ERKs), p38 MAP kinase and protein kinase B (Akt) in a frequency-dependent manner. Furthermore, the inhibition of the p38 pathway could block the frequency-induced phenotype modulation of VSMCs, but not inhibition of ERK or Akt pathways. These results indicate that the frequency of cyclic strain can result in the differentiated phenotype of VSMCs, and it is mediated at least partly by the activation of the p38 pathway.
Qu
Ming-Juan
MJ
Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China.
Liu
Bo
B
Wang
Han-Qin
HQ
Yan
Zhi-Qiang
ZQ
Shen
Bao-Rong
BR
Jiang
Zong-Lai
ZL
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D015153:Blotting, Western; D048430:Cell Shape; D048429:Cell Size; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010507:Periodicity; D010641:Phenotype; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013314:Stress, Mechanical; D014661:Vasoconstriction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D009124:Muscle Proteins; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases