期刊
FASEB JOURNAL
卷 20, 期 7, 页码 1006-+出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.05-4838fje
关键词
FGF; TGF beta; fibrosis
资金
- NCI NIH HHS [1-R24-CA095823] Funding Source: Medline
- NEI NIH HHS [R01 EY09414, R01 EY009414, R01 EY017030, F32 EY07049, P30 EY001867] Funding Source: Medline
Fibroblasts and myofibroblasts both participate in wound healing. Transforming growth factor beta (TGF beta) induces fibroblasts to differentiate into myofibroblasts, whereas fibroblast growth factor and heparin (FGF/ h) induce myofibroblasts to de-differentiate into fibroblasts. TGF beta induces expression of smooth muscle alpha actin (SM alpha A) and incorporation into in stress fibers, a phenotype of differentiated myofibroblasts. Additionally, TGF beta induces the expression of fibronectin and fibronectin integrins. Fibronectin-generated signals contribute to the TGF beta-mediated myofibroblast differentiation. Because fibronectin signals are transmitted through focal adhesion kinase (FAK), it was predicted that FAK would be essential to TGF beta-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 SM alpha A 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 beta-dependent myofibroblast differentiation. Instead, FAK was necessary for FGF/ h signaling in down-regulating expression of SM alpha A, which is synonymous with myofibroblast differentiation. FAK activation could contribute to regulating myofibroblast differentiation, thereby ameliorating fibrosis.
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