Induction of SM-alpha-actin expression by mechanical strain in adult vascular smooth muscle cells is mediated through activation of JNK and p38 MAP kinase.
Mechanical forces have direct effects on the growth and differentiation of vascular smooth muscle. The goal of this study was to examine the effects of cyclic mechanical strain on expression of smooth muscle-alpha-actin (SM-alpha-actin), a marker for the differentiated state of vascular smooth muscle, in cultured rat aortic smooth muscle cells (VSMC). Cells grown on dishes coated with either laminin or pronectin were subjected to mechanical strain and effects on expression of SM-alpha-actin were evaluated using the Flexercell Strain Unit. Application of mechanical strain to cells in full media increased SM-alpha-actin protein expression and promoter activity. This was not associated with any effect on growth. Mechanical strain increased activity of all three members of the MAP kinase family (ERKs, JNKs, and p38 MAP kinase), with similar kinetics. Inhibition of either JNKs or p38 MAP kinase blocked the strain-induced increase in SM-alpha-actin promoter activity, and expression of constitutively active forms of JNK or MKK6, a p38 kinase, increased promoter activity. These studies indicate that in adult VSMC, mechanical strain leads to increased expression of smooth muscle markers, resulting in a more contractile phenotype.
Tock
Jenny
J
Department of Pediatrics, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Box C-281, 4200 E. Ninth Ave., Denver, CO 80262, USA.
Van Putten
Vicki
V
Stenmark
Kurt R
KR
Nemenoff
Raphael A
RA
D000199:Actins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D013314:Stress, Mechanical; D048051:p38 Mitogen-Activated Protein Kinases
D000199:Actins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases