title: Mechanoregulation of the Myofibroblast in Wound Contraction, Scarring, and Fibrosis: Opportunities for New Therapeutic Intervention.
abstract: CONCLUSIONS
  Myofibroblasts are responsible for wound closure that occurs in healed acute wounds. However, their actions can result in disfiguring scar contractures, compromised organ function, and a tumor promoting stroma. Understanding the mechanisms regulating their contractile machinery, gene expression, and lifespan is essential to develop new therapies to control their function.
  
  
  BACKGROUND
  Mechanical stress and transforming growth factor beta-1 (TGF-β1) regulate myofibroblast differentiation from mesenchymal progenitors. As these precursor cells differentiate, they assemble a contractile apparatus to generate the force used to contract wounds. The mechanisms by which mechanical stress promote expression of contractile genes through the TGF-β1 and serum response factor pathways and offer therapeutic targets to limit myofibroblast function are being elucidated.
  
  
  RESULTS
  Emerging evidence suggests that the integration of mechanical cues with intracellular signaling pathways is critical to myofibroblast function via its effects on gene expression, cellular contraction, and paracrine signaling with neighboring cells. In addition, while apoptosis is clearly one pathway that can limit myofibroblast lifespan, recent data suggest that pathogenic myofibroblasts can become senescent and adopt a more beneficial phenotype, or may revert to a quiescent state, thereby limiting their function.
  
  
  CONCLUSIONS
  Given the important role that myofibroblasts play in pathologies as disparate as cutaneous scarring, organ fibrosis, and tumor progression, knowledge gained in the areas of intracellular signaling networks, mechanical signal transduction, extracellular matrix biology, and cell fate will support efforts to develop new therapies with a wide impact.
authors: Center for Cell Biology and Cancer Research , Albany Medical College, Albany, New York.
authors: Livingston
authors: L
authors: Van De Water
authors: Center for Cell Biology and Cancer Research , Albany Medical College, Albany, New York.
authors: Scott
authors: S
authors: Varney
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma.
authors: James J
authors: JJ
authors: Tomasek