title: Role of RhoA/ROCK-dependent actin contractility in the induction of tenascin-C by cyclic tensile strain.
abstract: In chick embryo fibroblasts, the mRNA for extracellular matrix protein tenascin-C is induced 2-fold by cyclic strain (10%, 0.3 Hz, 6 h). This response is attenuated by inhibiting Rho-dependent kinase (ROCK). The RhoA/ROCK signaling pathway is primarily involved in actin dynamics. Here, we demonstrate its crucial importance in regulating tenascin-C expression. Cyclic strain stimulated RhoA activation and induced fibroblast contraction. Chemical activators of RhoA synergistically enhanced the effects of cyclic strain on cell contractility. Interestingly, tenascin-C mRNA levels perfectly matched the extent of RhoA/ROCK-mediated actin contraction. First, RhoA activation by thrombin, lysophosphatidic acid, or colchicine induced tenascin-C mRNA to a similar extent as strain. Second, RhoA activating drugs in combination with cyclic strain caused a super-induction (4- to 5-fold) of tenascin-C mRNA, which was again suppressed by ROCK inhibition. Third, disruption of the actin cytoskeleton with latrunculin A abolished induction of tenascin-C mRNA by chemical RhoA activators in combination with cyclic strain. Lastly, we found that myosin II activity is required for tenascin-C induction by cyclic strain. We conclude that RhoA/ROCK-controlled actin contractility has a mechanosensory function in fibroblasts that correlates directly with tenascin-C gene expression. Previous RhoA/ROCK activation, either by chemical or mechanical signals, might render fibroblasts more sensitive to external tensile stress, e.g., during wound healing.
authors.affiliation: ITI-Research Institute for Dental and Skeletal Biology, University of Bern, Murtenstrasse 35, P.O. Box 54, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Sarasa-Renedo
authors.forename: Vildan
authors.initials: V
authors.lastname: Tunç-Civelek
authors.forename: Matthias
authors.initials: M
authors.lastname: Chiquet
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002642:Chick Embryo; D003238:Connective Tissue / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013314:Stress, Mechanical; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D013718:Tensile Strength / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000819:agonists / Q000378:metabolism*
chemical_list: D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019063:Tenascin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D024462:Myosin Type II; D020742:rhoA GTP-Binding Protein