FAK-dependent regulation of myofibroblast differentiation

Greenberg RS, Bernstein AM, Benezra M, Gelman IH, Taliana L, Masur SK
Source: FASEB J
Publication Date: (2006)
Issue: 20(7): 1006-8
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Embryonic fibroblast, mouse (MEF) immort
Species: mouse
Tissue Origin: embryo
Nucleofector® I/II/2b
Fibroblasts and myofibroblasts both participate in wound healing.Transforming growth factor beta (TGF) induces fibroblasts to( )differentiate into myofibroblasts, whereas fibroblast growth( )factor and heparin (FGF/h) induce myofibroblasts to "de-differentiate"( )into fibroblasts. TGF induces expression of smooth muscle alpha( )actin (SMA) and incorporation into in stress fibers, a phenotype( )of differentiated myofibroblasts. Additionally, TGF induces( )the expression of fibronectin and fibronectin integrins. Fibronectin-generated( )signals contribute to the TGF-mediated myofibroblast differentiation.( )Because fibronectin signals are transmitted through focal adhesion( )kinase (FAK), it was predicted that FAK would be essential to( )TGF-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 SMA in stress fibers even after treatment( )with FGF/h. Furthermore, both the surface expression of FGFRs( )and FGF signaling were greatly reduced in FAK-/- MEFs. We conclude( )that FAK does not contribute to TGF-dependent myofibroblast( )differentiation. Instead, FAK was necessary for FGF/h signaling( )in down-regulating expression of SMA, which is synonymous with( )myofibroblast differentiation. FAK activation could contribute( )to regulating myofibroblast differentiation, thereby ameliorating( )fibrosis.( ).