FAK-dependent regulation of myofibroblast differentiation

FASEB J. 2006 May;20(7):1006-8. doi: 10.1096/fj.05-4838fje. Epub 2006 Apr 3.


Fibroblasts and myofibroblasts both participate in wound healing. Transforming growth factor beta (TGFbeta) induces fibroblasts to differentiate into myofibroblasts, whereas fibroblast growth factor and heparin (FGF/h) induce myofibroblasts to "de-differentiate" into fibroblasts. TGFbeta induces expression of smooth muscle alpha actin (SMalphaA) and incorporation into in stress fibers, a phenotype of differentiated myofibroblasts. Additionally, TGFbeta induces the expression of fibronectin and fibronectin integrins. Fibronectin-generated signals contribute to the TGFbeta-mediated myofibroblast differentiation. Because fibronectin signals are transmitted through focal adhesion kinase (FAK), it was predicted that FAK would be essential to TGFbeta-mediated myofibroblast differentiation. To determine whether the FAK signaling pathway is required for myofibroblast differentiation, we used two approaches to decrease FAK in mouse embryo fibroblasts (MEFs): 1) FAK +/+ MEFs, in which FAK protein expression was greatly decreased by short hairpin RNA (shRNA), and 2) FAK -/- MEFs, which lack FAK. In both cases, the majority of cells were myofibroblasts, expressing SMalphaA in stress fibers even after treatment with FGF/h. Furthermore, both the surface expression of FGFRs and FGF signaling were greatly reduced in FAK -/- [corrected]MEFs. We conclude that FAK does not contribute to TGFbeta-dependent myofibroblast differentiation. Instead, FAK was necessary for FGF/h signaling in down-regulating expression of SMalphaA, which is synonymous with myofibroblast differentiation. FAK activation could contribute to regulating myofibroblast differentiation, thereby ameliorating fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblast Growth Factors / metabolism
  • Fibroblasts / metabolism*
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Deletion
  • Gene Expression Regulation
  • RNA Interference
  • Receptors, Fibroblast Growth Factor / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism


  • Actins
  • Receptors, Fibroblast Growth Factor
  • Transforming Growth Factor beta
  • Fibroblast Growth Factors
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases