Role of RhoA/ROCK-dependent actin contractility in the induction of tenascin-C by cyclic tensile strain

Exp Cell Res. 2006 May 1;312(8):1361-70. doi: 10.1016/j.yexcr.2005.12.025. Epub 2006 Jan 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Animals
  • Cell Line, Transformed
  • Cells, Cultured
  • Chick Embryo
  • Connective Tissue / metabolism*
  • Connective Tissue / ultrastructure
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Fibroblasts / metabolism*
  • Fibroblasts / ultrastructure
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Intracellular Signaling Peptides and Proteins
  • Mechanotransduction, Cellular / drug effects
  • Mechanotransduction, Cellular / physiology
  • Mice
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Myosin Type II / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Stress, Mechanical
  • Tenascin / genetics
  • Tenascin / metabolism*
  • Tensile Strength / physiology
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Wound Healing / drug effects
  • Wound Healing / physiology
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein / agonists
  • rhoA GTP-Binding Protein / metabolism*


  • Actins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Tenascin
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • Myosin Type II
  • rhoA GTP-Binding Protein